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Murto N, Lund T, Kautiainen H, Luoma K, Kerttula L. Comparison of lumbar disc degeneration grading between deep learning model SpineNet and radiologist: a longitudinal study with a 14-year follow-up. EUROPEAN SPINE JOURNAL : OFFICIAL PUBLICATION OF THE EUROPEAN SPINE SOCIETY, THE EUROPEAN SPINAL DEFORMITY SOCIETY, AND THE EUROPEAN SECTION OF THE CERVICAL SPINE RESEARCH SOCIETY 2025:10.1007/s00586-025-08900-2. [PMID: 40372457 DOI: 10.1007/s00586-025-08900-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/04/2024] [Revised: 02/07/2025] [Accepted: 04/28/2025] [Indexed: 05/16/2025]
Abstract
PURPOSE To assess the agreement between lumbar disc degeneration (DD) grading by the convolutional neural network model SpineNet and radiologist's visual grading. METHODS In a 14-year follow-up MRI study involving 19 male volunteers, lumbar DD was assessed by SpineNet and two radiologists using the Pfirrmann classification at baseline (age 37) and after 14 years (age 51). Pfirrmann summary scores (PSS) were calculated by summing individual disc grades. The agreement between the first radiologist and SpineNet was analyzed, with the second radiologist's grading used for inter-observer agreement. RESULTS Significant differences were observed in the Pfirrmann grades and PSS assigned by the radiologist and SpineNet at both time points. SpineNet assigned Pfirrmann grade 1 to several discs and grade 5 to more discs compared to the radiologists. The concordance correlation coefficients (CCC) of PSS between the radiologist and SpineNet were 0.54 (95% CI: 0.28 to 0.79) at baseline and 0.54 (0.27 to 0.80) at follow-up. The average kappa (κ) values of 0.74 (0.68 to 0.81) at baseline and 0.68 (0.58 to 0.77) at follow-up. CCC of PSS between the radiologists was 0.83 (0.69 to 0.97) at baseline and 0.78 (0.61 to 0.95) at follow-up, with κ values ranging from 0.73 to 0.96. CONCLUSION We found fair to substantial agreement in DD grading between SpineNet and the radiologist, albeit with notable discrepancies. These findings indicate that AI-based systems like SpineNet hold promise as complementary tools in radiological evaluation, including in longitudinal studies, but emphasize the need for ongoing refinement of AI algorithms.
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Affiliation(s)
- Niko Murto
- Department of Radiology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
- Department of Radiology, Helsinki University Central Hospital, PO Box 200, Helsinki, 00029 HUS, Finland.
| | - Teija Lund
- Department of Orthopaedics and Traumatology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
| | - Hannu Kautiainen
- Primary Health Care Unit, Finland and Folkhälsan Research Center, Kuopio University Hospital, Helsinki, Finland
| | - Katariina Luoma
- Department of Radiology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
| | - Liisa Kerttula
- Department of Radiology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
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Iwane N, Hashizume H, Murata S, Mure K, Oka H, Iidaka T, Teraguchi M, Nagata K, Ishimoto Y, Takami M, Tsutsui S, Iwasaki H, Tanaka S, Yamada H, Yoshimura N. Lumbar Disc Degeneration and Vertebral Fracture at the Thoracolumbar Junction Are Risk Factors for Chronic Low Back Pain With Disability: Seven Years' Follow-Up of the Wakayama Spine Study. Cureus 2025; 17:e84291. [PMID: 40524991 PMCID: PMC12169606 DOI: 10.7759/cureus.84291] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 05/17/2025] [Indexed: 06/19/2025] Open
Abstract
Introduction Low back pain (LBP) is the leading cause of disability worldwide, with its burden increasing in aging societies such as Japan. Although degenerative spinal changes like lumbar disc degeneration (DD), vertebral fractures, and lumbar spinal stenosis (LSS) are frequently identified on MRI, their combined longitudinal impact on disabling chronic low back pain (DCLBP) remains unclear. The aim of this study was to identify baseline MRI-detected lumbar spinal changes that independently predict disabling chronic low back pain in a general Japanese population. Methods This population-based longitudinal study included 663 community-dwelling Japanese adults from the Wakayama Spine Study, a sub-cohort of the nationwide Research on Osteoarthritis/Osteoporosis Against Disability (ROAD) study. Baseline whole-spine MRI and clinical assessments were conducted between 2008 and 2009, with a seven-year follow-up from 2015 to 2016. MRI findings included Pfirrmann-graded lumbar DD, Genant-graded vertebral fractures at T11-L1, and Suri-graded LSS. The primary outcome was DCLBP, defined as LBP lasting more than three months and an Oswestry Disability Index (ODI) score ≥21%. Multivariate logistic regression was used to identify independent predictors of DCLBP. Results Of 653 participants who completed follow-up with valid ODI responses, 91 (13.9%) had DCLBP. Older age (OR: 1.07 per year, p < 0.0001), female sex (OR: 3.69, p < 0.0001), higher BMI (OR: 1.11 per kg/m², p < 0.0001), greater vertebral fracture burden (OR: 1.32 per grade point, p = 0.0024), and more severe lumbar DD (OR: 1.14 per grade point, p = 0.0305) were independently associated with DCLBP. Conclusion Lumbar DD, vertebral fractures at T11-L1, and LSS are independent risk factors for disabling chronic LBP in the general population. These findings underscore the importance of comprehensive MRI-based spinal assessment in identifying high-risk individuals for early intervention in aging societies.
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Affiliation(s)
- Naomi Iwane
- School of Health and Nursing Science, Wakayama Medical University, Wakayama, JPN
| | - Hiroshi Hashizume
- School of Health and Nursing Science, Wakayama Medical University, Wakayama, JPN
- Department of Orthopaedic Surgery, Wakayama Medical University, Wakayama, JPN
| | - Shizumasa Murata
- Department of Orthopaedic Surgery, Wakayama Medical University, Wakayama, JPN
| | - Kanae Mure
- Department of Public Health, Wakayama Medical University, Wakayama, JPN
| | - Hiroyuki Oka
- Division of Musculoskeletal AI System Development, Faculty of Medicine, The University of Tokyo, Tokyo, JPN
| | - Toshiko Iidaka
- Department of Preventive Medicine for Locomotive Organ Disorders, 22nd Century Medical and Research Center, The University of Tokyo, Tokyo, JPN
| | - Masatoshi Teraguchi
- Department of Orthopaedic Surgery, Wakayama Medical University, Wakayama, JPN
| | - Keiji Nagata
- Department of Orthopaedic Surgery, Wakayama Medical University, Wakayama, JPN
| | - Yuyu Ishimoto
- Department of Orthopaedic Surgery, Wakayama Medical University, Wakayama, JPN
| | - Masanari Takami
- Department of Orthopaedic Surgery, Wakayama Medical University, Wakayama, JPN
| | - Shunji Tsutsui
- Department of Orthopaedic Surgery, Wakayama Medical University, Wakayama, JPN
| | - Hiroshi Iwasaki
- Department of Orthopaedic Surgery, Wakayama Medical University, Wakayama, JPN
| | - Sakae Tanaka
- Department of Orthopaedic Surgery, Faculty of Medicine, The University of Tokyo, Tokyo, JPN
| | - Hiroshi Yamada
- Department of Orthopaedic Surgery, Wakayama Medical University, Wakayama, JPN
| | - Noriko Yoshimura
- Department of Preventive Medicine for Locomotive Organ Disorders, 22nd Century Medical and Research Center, The University of Tokyo, Tokyo, JPN
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Hua Z, Zhao Y, Zhang M, Wang Y, Feng H, Wei X, Wu X, Chen W, Xue Y. Research progress on intervertebral disc repair strategies and mechanisms based on hydrogel. J Biomater Appl 2025; 39:1121-1142. [PMID: 39929142 DOI: 10.1177/08853282251320227] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/03/2025]
Abstract
Intervertebral disc degeneration (IDD) arises from a complex interplay of genetic, environmental, and age-related factors, culminating in a spectrum of low back pain (LBP) disorders that exert significant societal and economic impact. The present therapeutic landscape for IDD poses formidable clinical hurdles, necessitating the exploration of innovative treatment modalities. The hydrogel, as a biomaterial, exhibits superior biocompatibility compared to other biomaterials such as bioceramics and bio-metal materials. It also demonstrates mechanical properties closer to those of natural intervertebral discs (IVDs) and favorable biodegradability conducive to IVD regeneration. Therefore, it has emerged as a promising candidate material in the field of regenerative medicine and tissue engineering for treating IDD. Hydrogels have made significant strides in the field of IDD treatment. Particularly, injectable hydrogels not only provide mechanical support but also enable controlled release of bioactive molecules, playing a crucial role in mitigating inflammation and promoting extracellular matrix (ECM) regeneration. Furthermore, the ability of injectable hydrogels to achieve minimally invasive implantation helps minimize tissue damage. This article initially provides a concise exposition of the structure and function of IVD, the progression of IDD, and delineates extant clinical interventions for IDD. Subsequently, it categorizes hydrogels, encapsulates recent advancements in biomaterials and cellular therapies, and delves into the mechanisms through which hydrogels foster disc regeneration. Ultimately, the article deliberates on the prospects and challenges attendant to hydrogel therapy for IDD.
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Affiliation(s)
- Zekun Hua
- College of Artificial Intelligence, Taiyuan University of Technology, Taiyuan, China
| | - Yinuo Zhao
- College of Artificial Intelligence, Taiyuan University of Technology, Taiyuan, China
| | - Meng Zhang
- College of Artificial Intelligence, Taiyuan University of Technology, Taiyuan, China
| | - Yanqin Wang
- College of Artificial Intelligence, Taiyuan University of Technology, Taiyuan, China
| | - Haoyu Feng
- Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Third Hospital of Shanxi Medical University, Taiyuan, China
| | - Xiaochun Wei
- Shanxi Key Laboratory of Bone and Soft Tissue Injury Repair, Department of Orthopaedics, The Second Hospital of Shanxi Medical University, Taiyuan, China
| | - Xiaogang Wu
- College of Artificial Intelligence, Taiyuan University of Technology, Taiyuan, China
- Shanxi Key Laboratory of Bone and Soft Tissue Injury Repair, Department of Orthopaedics, The Second Hospital of Shanxi Medical University, Taiyuan, China
| | - Weiyi Chen
- College of Artificial Intelligence, Taiyuan University of Technology, Taiyuan, China
| | - Yanru Xue
- College of Artificial Intelligence, Taiyuan University of Technology, Taiyuan, China
- Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Third Hospital of Shanxi Medical University, Taiyuan, China
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Keskimölö T, Oura P, Honkanen T, Niinimäki J, Sovelius R, Leino T, Karppinen J. Association Between Cumulative G-force Exposure and Cervical Spine Degenerative Changes. Mil Med 2025; 190:e930-e937. [PMID: 39312403 PMCID: PMC12016033 DOI: 10.1093/milmed/usae452] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/09/2024] [Revised: 08/11/2024] [Accepted: 09/12/2024] [Indexed: 09/25/2024] Open
Abstract
INTRODUCTION Fighter pilots work in a unique environment and are subject to high G-force loads under simultaneous head movements. Neck pain is reported to be a common health problem among fighter pilots leading to time lost flying and flight duty limitations. The present study aimed to find out if differences in early military flight career G-force exposure levels could increase the risk for degenerative changes in the cervical spine. MATERIALS AND METHODS The study population consisted of 56 20-year-old Finnish Air Force male fighter pilot cadets, who underwent MRI of the cervical spine at baseline and after 5 years. During follow-up, the G-force exposure was measured using the individual Fatigue Index (FI) recordings. The FI data were collected from each flight with BAE Hawks and is determined by the number of times certain levels of G-forces are exceeded during the flights. The incidence or progression of each degenerative change was compared to individual FI values using Pearson correlation coefficients. RESULTS The pilots flew on average 220 (±21) hours with high performance aircraft during follow-up, resulting in an average FI of 1.98 (±0.47). A statistically significant progression was found in intervertebral disc (IVD) degeneration sum score with no correlation to corresponding FI values. A statistically significant increase was also found in the prevalence of IVD herniations with a negative correlation with FI values. Other degenerative cervical spine changes did not progress or did not correlate with corresponding FI values. CONCLUSIONS The prevalence of IVD degeneration and IVD herniations increases in the early phases of fighter pilots' career. Only the incidence of IVD herniations correlated with FI values and the correlation was negative. The negative correlation may be attributed to avoidance behavior due to neck pain, which was not measured in our study, or other unmeasured confounding factors. This was the first study to compare individual G-force exposure levels to high-quality MRI data over a follow-up of several years. Finnish fighter pilots are known to report increasing cervical symptoms during the Hawk training phase, but longer follow-up periods are likely needed to determine the association between G-force exposure levels and cervical degenerative changes.
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Affiliation(s)
- Tuomas Keskimölö
- Faculty of Medicine, University of Oulu, Oulu 90220, Finland
- Research and Development Section, Centre for Military Medicine, Finnish Defence Forces, Helsinki 00290, Finland
| | - Petteri Oura
- Medical Research Center Oulu, Oulu University Hospital, Oulu 90220, Finland
| | - Tuomas Honkanen
- Aeromedical Centre, Centre for Military Medicine, Finnish Defence Forces, Helsinki 00301, Finland
- Department of Leadership and Military Pedagogy, National Defence University, Helsinki 00860, Finland
| | - Jaakko Niinimäki
- Medical Research Center Oulu, Oulu University Hospital, Oulu 90220, Finland
- Research Unit of Health Sciences and Technology, University of Oulu, Oulu 90220, Finland
| | - Roope Sovelius
- Aeromedical Centre, Centre for Military Medicine, Finnish Defence Forces, Helsinki 00301, Finland
| | - Tuomo Leino
- Department of Leadership and Military Pedagogy, National Defence University, Helsinki 00860, Finland
- Air Force Command Finland, Finnish Air Force, Tikkakoski 41161, Finland
| | - Jaro Karppinen
- Research Unit of Health Sciences and Technology, University of Oulu, Oulu 90220, Finland
- Oulu Regional Office, Finnish Institute of Occupational Health, Oulu 90220, Finland
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Yeshna, Singh M, Monika, Kumar A, Garg V, Jhawat V. Pathophysiology and emerging therapeutic strategies for cervical spondylosis: The role of pro-inflammatory mediators, kinase inhibitors, and Organogel based drug delivery systems. Int Immunopharmacol 2025; 151:114350. [PMID: 40010157 DOI: 10.1016/j.intimp.2025.114350] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/30/2024] [Revised: 02/20/2025] [Accepted: 02/20/2025] [Indexed: 02/28/2025]
Abstract
Cervical spondylosis is a prevalent ailment characterized by chronic wear and degenerative changes affecting the cervical spine, leading to various clinical syndromes such as axial neck pain, cervical myelopathy, and cervical radiculopathy. The pathophysiology of the development of cervical alterations is multifaceted, with alterations in the normal physiology and pathogenesis of intervertebral disc degeneration. The involvement of pro-inflammatory mediators, such as interleukin-1, tumor necrosis factor-α, interleukin-4, interleukin-6, and interleukin-10, in the pathological processes associated with intervertebral disc degeneration offers potential therapeutic targets. The review also introduces kinase inhibitors as potential treatments for cervical spondylosis. Protein kinase inhibitors, including mitogen-activated protein kinase (MAPK), Janus kinase (JAK), and spleen tyrosine kinase (SYK), are explored for their anti-inflammatory properties. The article discusses their potential in modulating inflammatory signaling cascades and presents them as attractive candidates for treating immune-mediated disorders. Inhibitors of Nuclear Factor-κB, p38 MAPK, Jun-N terminal kinase (JNK), and Extracellular signal-regulated kinase (ERK) have shown efficacy in suppressing inflammatory responses, offering potential avenues for intervention in this prevalent condition. Organogels are semi-solid materials formed by trapping an organic solvent within a three-dimensional cross-linked network. They hold considerable potential in drug delivery, especially in enhancing drug solubility, facilitating controlled release, and improving skin penetration. These properties of organogels can help treat or alleviate the symptoms of cervical spondylosis.
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Affiliation(s)
- Yeshna
- Department of Pharmaceutical Science, School of Healthcare and Allied Science, GD Goenka University, Gurugram, Haryana, India
| | - Monika Singh
- Department of Pharmaceutical Science, School of Healthcare and Allied Science, GD Goenka University, Gurugram, Haryana, India
| | - Monika
- Department of Pharmaceutical Science, School of Healthcare and Allied Science, GD Goenka University, Gurugram, Haryana, India
| | - Ashok Kumar
- Faculty of Pharmacy, Kalinga University, Naya Raipur, Chhattisgarh, India
| | - Vandana Garg
- Department of Pharmaceutical Science, MD University, Rohtak, India
| | - Vikas Jhawat
- Department of Pharmaceutical Science, School of Healthcare and Allied Science, GD Goenka University, Gurugram, Haryana, India.
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Fitzgerald A, McCool R, Carr E, Miller P, Reddish K, Lohr CC, Annoni E, Lawrence B. A systematic review of bone graft products used in lumbar interbody fusion procedures for degenerative disc disease. NORTH AMERICAN SPINE SOCIETY JOURNAL 2025; 21:100579. [PMID: 39917175 PMCID: PMC11800106 DOI: 10.1016/j.xnsj.2024.100579] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 08/15/2024] [Revised: 12/04/2024] [Accepted: 12/26/2024] [Indexed: 02/09/2025]
Abstract
Background Degenerative disc disease (DDD) is associated with chronic lower back pain that may have impacts on individual's quality of life and functional ability. Lumbar interbody fusion can be carried out with a variety of bone grafting products, the choice depends on several factors including the patient, site, procedure, cost and indication. This systematic review (SR) intends to validate and consolidate the existing evidence base supporting bone graft materials related to lumbar interbody fusion procedures for DDD, specifically anterior lumbar interbody fusion (ALIF) and oblique lumbar interbody fusion (OLIF). Methods An SR was conducted in February 2023. Clinical and economic studies of adults with DDD in regions L2 to S1 undergoing lumbar interbody fusion with Infuse™, allograft, synthetic bone grafts, demineralized bone matrices or cell-based matrices were eligible for inclusion. Results Twenty-one studies (reported in 25 publications) were included in the review. Eighteen studies (reported in 22 publications) reported clinical outcomes, while 4 studies reported economic outcomes. Nine studies (in 5 publications) investigated Infuse™, including 3 randomized controlled trials (RCTs), one cohort study and 4 case series. Ten studies investigated allograft bone, bone harvested from the vertebral spur combined with apacerum powder, or tricalcium phosphate soaked in autologous bone marrow aspirate, including one RCT, 2 cohort studies, and 7 case series. Conclusions The SR shows that Infuse™ offers comparable results to iliac crest bone graft with the benefit of not requiring harvested bone and offers significant benefits in surgical time and blood loss. There is a lack of comparative evidence for any other bone grafts identified in this SR, highlighting the need for further well-designed studies to be conducted in this area.
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Affiliation(s)
- Anita Fitzgerald
- York Health Economics Consortium, Enterprise House, University of York, York, United Kingdom
| | - Rachael McCool
- York Health Economics Consortium, Enterprise House, University of York, York, United Kingdom
| | - Emma Carr
- York Health Economics Consortium, Enterprise House, University of York, York, United Kingdom
| | - Paul Miller
- York Health Economics Consortium, Enterprise House, University of York, York, United Kingdom
| | - Katie Reddish
- York Health Economics Consortium, Enterprise House, University of York, York, United Kingdom
| | - Cynthia C Lohr
- Medtronic, Office of Medical Affairs, Memphis, TN, United States
| | - Elena Annoni
- Health Economics, Policy & Reimbursement, Medtronic International Trading Sàrl, 1131 Tolochenaz, Switzerland
| | - Brandon Lawrence
- Department of Orthopaedics, University of Utah, UT, United States
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Chiu AP, Lesnak J, Gabriel K, Price TJ, Arendt-Nielsen L, Bobos P, Curatolo M. Human molecular mechanisms of discogenic low back pain: A scoping review. THE JOURNAL OF PAIN 2025; 27:104693. [PMID: 39374801 PMCID: PMC11807758 DOI: 10.1016/j.jpain.2024.104693] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/12/2024] [Revised: 09/25/2024] [Accepted: 10/02/2024] [Indexed: 10/09/2024]
Abstract
The limited understanding of the mechanisms underlying human discogenic low back pain (DLBP) has hampered the development of effective treatments. While there is much research on disc degeneration, the association between degeneration and pain is weak. Therefore, there is an urgent need to identify pain-inducing molecular mechanism to facilitate the development of mechanism-specific therapeutics. This scoping review aims to determine the current knowledge of molecular mechanisms associated with human DLBP. A systematic search on CENTRAL, CINAHL, Citation searching, ClinicalTrials.gov, Embase, Google Scholar, MEDLINE, PsycINFO, PubMed, Scopus, Web of Science, and World Health Organization was performed. Studies with human DLBP as diagnosed by discography or imaging that analyzed human disc tissues and reported pain-related outcomes were included, and those on predominant radicular pain were excluded. The search returned 6012 studies. Most studies did not collect pain-related outcomes. Those that included pain assessment relied on self-report of pain intensity and disability. Six studies qualified for data extraction and synthesis. The main molecular mechanisms associated with DLBP were the expressions of nociceptive neuropeptides and cytokines, particularly TNF-αdue to its strong association with pain outcomes. Activation of NF-κB signaling pathway, alterations in adrenoceptor expressions, and increase in reactive oxygen species (ROS) were also associated with DLBP through regulation of pro-inflammatory factors and pain-related neuropeptides. Current evidence converges to TNF-α, NF-κB signaling, and ROS-induced pro-inflammation. Major weaknesses in the current literature are the focus on degeneration without pain phenotyping, and lack of association of molecular findings with pain outcomes. PERSPECTIVE: This scoping review identified TNF-α, NF-κB signaling, and ROS-induced pro-inflammation as relevant mechanisms of human discogenic low back pain. Major weaknesses in the current literature are the focus on degeneration without pain phenotyping, and lack of association of molecular findings with pain outcomes.
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Affiliation(s)
- Abby P Chiu
- Department of Anesthesiology and Pain Medicine, University of Washington School of Medicine, Seattle, WA, USA; Clinical Learning, Evidence And Research (CLEAR) Center for Musculoskeletal Research, University of Washington, Seattle, WA, USA
| | - Joseph Lesnak
- Department of Neuroscience and Center for Advanced Pain Studies, University of Texas at Dallas, USA
| | - Katherin Gabriel
- Department of Neuroscience and Center for Advanced Pain Studies, University of Texas at Dallas, USA
| | - Theodor J Price
- Department of Neuroscience and Center for Advanced Pain Studies, University of Texas at Dallas, USA
| | - Lars Arendt-Nielsen
- Center for Neuroplasticity and Pain (CNAP), SMI, Medical School, Aalborg University, Denmark; Department of Gastroenterology & Hepatology, Mech-Sense, Clinical Institute, Aalborg University Hospital, Aalborg, Denmark; Steno Diabetes Center North Denmark, Clinical Institute, Aalborg University Hospital, Aalborg, Denmark
| | - Pavlos Bobos
- School of Physical Therapy, Western University, London, Ontario, Canada; Department of Epidemiology and Biostatistics, Western University, London, Ontario, Canada
| | - Michele Curatolo
- Department of Anesthesiology and Pain Medicine, University of Washington School of Medicine, Seattle, WA, USA; Clinical Learning, Evidence And Research (CLEAR) Center for Musculoskeletal Research, University of Washington, Seattle, WA, USA.
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Bassani T, Colombini A, Pallotta L, Sconfienza LM, Albano D, Brayda-Bruno M. Association between MRI measurements of lumbar spine alterations and self-reported outcomes of pain and disability in subjects with non-specific low back pain. EUROPEAN SPINE JOURNAL : OFFICIAL PUBLICATION OF THE EUROPEAN SPINE SOCIETY, THE EUROPEAN SPINAL DEFORMITY SOCIETY, AND THE EUROPEAN SECTION OF THE CERVICAL SPINE RESEARCH SOCIETY 2024; 33:4572-4580. [PMID: 39164509 DOI: 10.1007/s00586-024-08449-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/21/2024] [Revised: 06/21/2024] [Accepted: 08/12/2024] [Indexed: 08/22/2024]
Abstract
PURPOSE This study aims to elucidate the association between MRI measurements of spine alterations and self-reported outcomes of pain and disability in individuals with non-specific low back pain, using a comprehensive perspective based on machine learning algorithm. METHODS 246 consecutive subjects were assessed. Pain severity in cervical, lumbar, and leg regions was determined using visual analogue scale, and functional disability was acquired by Oswestry Disability Index. Sagittal and axial MRI scans of the thoracolumbar spine were evaluated. Severity of disc degeneration, spinal canal stenosis, and presence of vertebral endplate lesions based on two different classification schemes involving the extent and the shape of defects were quantified at the levels from T12L1 to L5S1. The following parameters describing the lumbar region as a whole were calculated: maximum value along spinal levels, sum of values along levels, number of levels characterized by severe condition. The association with pain and disability was assessed by generalized multiple linear regression modelling. RESULTS Disc degeneration was identified as a predictor of disability and partially of pain, whereas canal stenosis was found associated with changes in pain in the leg region. Partial correlation values ranged from 0.11 to 0.32. Endplate lesions did not show significant associations. CONCLUSION A partial association between MRI measurements and self-reported outcomes of pain and disability was confirmed. Disc degeneration was the most correlated with the reported indexes, while canal stenosis mainly affected the pain levels in the leg region. The presence of endplate lesions did not demonstrate any significant relationships.
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Affiliation(s)
- Tito Bassani
- IRCCS Istituto Ortopedico Galeazzi, Milan, Italy.
| | | | | | - Luca Maria Sconfienza
- IRCCS Istituto Ortopedico Galeazzi, Milan, Italy
- Department of Biomedical Sciences for Health, University of Milan, Milan, Italy
| | - Domenico Albano
- IRCCS Istituto Ortopedico Galeazzi, Milan, Italy
- Department of Biomedical, Surgical, and Dental Sciences, University of Milan, Milan, Italy
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Duran Taş N, Sonel Tur B, Ergüder Bİ, Durmaz M. The relationship of serum adiponectin and leptin levels with pain, function and intervertebral disc degeneration in patients with chronic low back pain. Turk J Phys Med Rehabil 2024; 70:468-475. [PMID: 40028415 PMCID: PMC11868858 DOI: 10.5606/tftrd.2024.14272] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/18/2023] [Accepted: 01/19/2024] [Indexed: 03/05/2025] Open
Abstract
Objectives The aim of this study was to investigate the relationship between serum adiponectin and leptin levels, which are cytokines released from fatty tissue, and pain, function and intervertebral disc degeneration (IVDD). Patients and methods Between January 2018 and November 2019, a total of 85 patients (34 males, 51 females; mean age: 42.1±10.7 years; range, 18 to 62 years) who were diagnosed with IVDD and 84 healthy volunteers (34 males, 50 females; mean age: 41.9±10.7 years; range, 22 to 64 years) were included in this cross-sectional study. The Visual Analog Scale (VAS, 0-10 cm) and Oswestry Disability Index (ODI) scales were used in the patient group. Serum adiponectin and leptin levels were measured in all participants. The grading of IVDD was determined using the Pfirrmann Classification. Results There was no significant difference in serum adiponectin (p=0.35) and leptin (p=0.19) levels between the patient group and the control group. No relationship was found between serum adiponectin and leptin levels and pain intensity (VAS), pain duration, and disability (ODI) in patients with low back pain. No relationship was found between the severity of IVDD as evidenced by magnetic resonance imaging (MRI) and adiponectin (p=0.18) and leptin (p=0.11) levels. There was a positive correlation between the severity of disc degeneration and body mass index (r=0.35, p=0.008) and waist circumference (r=0.34, p=0.01). Conclusion Serum adipokine levels were not associated with low back pain symptoms and IVDD severity as evidenced by MRI. These findings suggest that the effects of obesity on chronic low back pain and disc degeneration cannot be explained by systemic inflammatory effects alone.
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Affiliation(s)
- Nurcan Duran Taş
- Department of Physical Medicine and Rehabilitation, Ankara University Faculty of Medicine, Ankara, Türkiye
| | - Birkan Sonel Tur
- Department of Physical Medicine and Rehabilitation, Ankara University Faculty of Medicine, Ankara, Türkiye
| | - Berrin İmge Ergüder
- Department of Biochemistry, Ankara University Faculty of Medicine, Ankara, Türkiye
| | - Mustafa Durmaz
- Department of Biochemistry, Ankara University Faculty of Medicine, Ankara, Türkiye
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Elmounedi N, Bahloul W, Keskes H. Current Therapeutic Strategies of Intervertebral Disc Regenerative Medicine. Mol Diagn Ther 2024; 28:745-775. [PMID: 39158834 DOI: 10.1007/s40291-024-00729-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 06/30/2024] [Indexed: 08/20/2024]
Abstract
Intervertebral disc degeneration (IDD) is one of the most frequent causes of low back pain. No treatment is currently available to delay the progression of IDD. Conservative treatment or surgical interventions is only used to target the symptoms of IDD rather than treat the underlying cause. Currently, numerous potential therapeutic strategies are available, including molecular therapy, gene therapy, and cell therapy. However, the hostile environment of degenerated discs is a major problem that has hindered the clinical applicability of such approaches. In this regard, the design of drugs using alternative delivery systems (macro-, micro-, and nano-sized particles) may resolve this problem. These can protect and deliver biomolecules along with helping to improve the therapeutic effect of drugs via concentrating, protecting, and prolonging their presence in the degenerated disc. This review summarizes the research progress of diagnosis and the current options for treating IDD.
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Affiliation(s)
- Najah Elmounedi
- Cell Therapy and Experimental Surgery of Musculoskeletal System LR18SP11 Lab, Sfax Faculty of Medicine, Majida Boulila Road, 3029, Sfax, Tunisia.
| | - Walid Bahloul
- Cell Therapy and Experimental Surgery of Musculoskeletal System LR18SP11 Lab, Sfax Faculty of Medicine, Majida Boulila Road, 3029, Sfax, Tunisia
- Department of Orthopedics and Traumatology, CHU Habib Bourguiba, Sfax, Tunisia
| | - Hassib Keskes
- Cell Therapy and Experimental Surgery of Musculoskeletal System LR18SP11 Lab, Sfax Faculty of Medicine, Majida Boulila Road, 3029, Sfax, Tunisia
- Department of Orthopedics and Traumatology, CHU Habib Bourguiba, Sfax, Tunisia
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11
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Yıldırım Uslu E, Gülkesen A, Akgol G, Alkan G, Poyraz AK, İlhan N. Serum Endothelin-1 Level Can Reflect the Degree of Lumbar Degeneration: A Cross-Sectional Study. Cureus 2024; 16:e59966. [PMID: 38854285 PMCID: PMC11162144 DOI: 10.7759/cureus.59966] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 05/09/2024] [Indexed: 06/11/2024] Open
Abstract
Background Endothelin-1 (ET-1) is an agent closely associated with inflammation and has recently been recognized as a significant factor in degenerative processes. This study aimed to investigate the correlation between serum ET-1 level and radiological and clinical manifestations of lumbar disc herniation (LDH) and intervertebral disc degeneration (IDD) pathologies. Methodology The study was conducted with 50 healthy controls and 50 LDH patients. The pain level of the patients was analyzed with the Visual Analog Scale (VAS), and their functionality was analyzed with the Oswestry Disability Index (ODI). The disc degeneration and disc herniation grades were determined using magnetic resonance imaging. Serum ET-1 levels of the participants were measured using the enzyme-linked immunosorbent assay method. Results ET-1 level was significantly higher in the patient group compared to the controls (p < 0.01). A positive correlation was determined between serum ET-1 level and Pfirrmann grade in the patient group (p < 0.01). No correlation was determined between the MacNab grade, VAS, and ODI scores and ET-1 (p = 0.397, p = 0.137, and p = 0.208, respectively). There was no significant difference between the serum ET-1 levels of the patients with or without neurological deficits (p = 0.312). Conclusions The correlation between the serum ET-1 levels and IDD grade suggested that the former could serve as a biomarker to determine the degree of degeneration in the future. However, further research is required to determine the underlying mechanisms.
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Affiliation(s)
- Emine Yıldırım Uslu
- Physical Medicine and Rehabilitation, Elazığ Fethi Sekin City Hospital, Elazig, TUR
| | - Arif Gülkesen
- Physical Medicine and Rehabilitation, Firat University, Elazig, TUR
| | - Gurkan Akgol
- Physical Medicine and Rehabilitation, Firat University Hospital, Elazig, TUR
| | - Gökhan Alkan
- Physical Medicine and Rehabilitation, Firat University, Elazig, TUR
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12
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Pontén S, Lagerbäck T, Blomé S, Jensen K, Skorpil M, Gerdhem P. Lumbar degeneration and quality of life in patients with lumbar disc herniation: a case-control long-term follow-up study. Acta Orthop 2024; 95:92-98. [PMID: 38305634 PMCID: PMC10836153 DOI: 10.2340/17453674.2024.39944] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/12/2023] [Accepted: 01/03/2024] [Indexed: 02/03/2024] Open
Abstract
BACKGROUND AND PURPOSE Adults treated surgically for lumbar disc herniation in adolescence have a higher degree of lumbar disc degeneration than controls. We aimed to establish whether the degree of lumbar degeneration differs at diagnosis or at follow-up between surgically and non-surgically treated individuals. METHODS We identified individuals with a lumbar disc herniation in adolescence diagnosed with magnetic resonance imaging (MRI) and contacted them for follow-up MRI. Lumbar degeneration was assessed according to Pfirrmann, Modic, and total end plate score (TEP score). Patient-reported outcome measures at follow-up comprised the Oswestry Disability Index (ODI), EQ-5D-3-level version, 36-Item Short Form Health Survey (SF-36), and Visual Analogue Scale (VAS) for back and leg pain. Fisher's exact test, Mann-Whitney U tests, Wilcoxon tests, and logistic regression were used for statistical analysis. RESULTS MRIs were available at diagnosis and after a mean of 11.9 years in 17 surgically treated individuals and 14 non-surgically treated individuals. Lumbar degeneration was similar at diagnosis (P = 0.2) and at follow-up, with the exception of higher TEP scores in surgically treated individuals at levels L4-L5 and L5-S1 at follow-up (P ≤ 0.03), but this difference did not remain after adjustment for age and sex (P ≥ 0.8). There were no significant differences in patient-reported outcome measures between the groups at follow-up (all P ≥ 0.2). CONCLUSION Adolescents with a lumbar disc herniation have, irrespective of treatment, a similar degree of lumbar degeneration at the time of diagnosis, and similar lumbar degeneration and patient-reported outcomes at long-term follow-up.
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Affiliation(s)
- Sebastian Pontén
- Department of Orthopaedics and Hand Surgery, Uppsala University Hospital, Uppsala; Department of Clinical Science, Intervention and Technology (CLINTEC), Karolinska Institutet, Stockholm
| | - Tobias Lagerbäck
- Department of Clinical Science, Intervention and Technology (CLINTEC), Karolinska Institutet, Stockholm
| | - Sebastian Blomé
- Department of Clinical Neuroscience, Division of Neuro, Karolinska Institutet, Stockholm
| | - Karin Jensen
- Department of Clinical Neuroscience, Division of Neuro, Karolinska Institutet, Stockholm
| | - Mikael Skorpil
- Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm; Department of Neuroradiology, Karolinska University Hospital, Stockholm
| | - Paul Gerdhem
- Department of Orthopaedics and Hand Surgery, Uppsala University Hospital, Uppsala; Department of Clinical Science, Intervention and Technology (CLINTEC), Karolinska Institutet, Stockholm; Department of Surgical Sciences, Uppsala University, Uppsala, Sweden.
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13
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Camino-Willhuber G, Schönnagel L, Caffard T, Zhu J, Tani S, Chiapparelli E, Arzani A, Shue J, Duculan R, Bendersky M, Zelenty WD, Sokunbi G, Lebl DR, Cammisa FP, Girardi FP, Mancuso CA, Hughes AP, Sama AA. Severe Intervertebral Vacuum Phenomenon is Associated With Higher Preoperative Low Back Pain, ODI, and Indication for Fusion in Patients With Degenerative Lumbar Spondylolisthesis. Clin Spine Surg 2024; 37:E1-E8. [PMID: 37651562 DOI: 10.1097/bsd.0000000000001510] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/22/2023] [Accepted: 07/19/2023] [Indexed: 09/02/2023]
Abstract
STUDY DESIGN Retrospective study of prospective collected data. OBJECTIVE To analyze the association between intervertebral vacuum phenomenon (IVP) and clinical parameters in patients with degenerative spondylolisthesis. SUMMARY OF BACKGROUND DATA IVP is a sign of advanced disc degeneration. The correlation between IVP severity and low back pain in patients with degenerative spondylolisthesis has not been previously analyzed. METHODS We retrospectively analyzed patients with degenerative spondylolisthesis who underwent surgery. Vacuum phenomenon was measured on computed tomography scan and classified into mild, moderate, and severe. A lumbar vacuum severity (LVS) scale was developed based on vacuum severity. The associations between IVP at L4/5 and the LVS scale, preoperative and postoperative low back pain, as well as the Oswestry Disability Index was assessed. The association of IVP at L4/5 and the LVS scale and surgical decision-making, defined as decompression alone or decompression and fusion, was assessed through univariable logistic regression analysis. RESULTS A total of 167 patients (52.7% female) were included in the study. The median age was 69 years (interquartile range 62-72). Overall, 100 (59.9%) patients underwent decompression and fusion and 67 (40.1%) underwent decompression alone. The univariable regression demonstrated a significantly increased odds ratio (OR) for back pain in patients with more severe IVP at L4/5 [OR=1.69 (95% CI 1.12-2.60), P =0.01]. The univariable regressions demonstrated a significantly increased OR for increased disability with more severe L4/L5 IVP [OR=1.90 (95% CI 1.04-3.76), P =0.04] and with an increased LVS scale [OR=1.17 (95% CI 1.02-1.35), P =0.02]. IVP severity of the L4/L5 were associated with higher indication for fusion surgery. CONCLUSION Our study showed that in patients with degenerative spondylolisthesis undergoing surgery, the severity of vacuum phenomenon at L4/L5 was associated with greater preoperative back pain and worse Oswestry Disability Index. Patients with severe IVP were more likely to undergo fusion.
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Affiliation(s)
- Gaston Camino-Willhuber
- Department of Orthopaedic Surgery, Hospital for Special Surgery, Weill Cornell Medicine, New York City, NY
| | - Lukas Schönnagel
- Department of Orthopaedic Surgery, Hospital for Special Surgery, Weill Cornell Medicine, New York City, NY
- Center for Musculoskeletal Surgery, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität Zu Berlin, Berlin
| | - Thomas Caffard
- Department of Orthopaedic Surgery, Hospital for Special Surgery, Weill Cornell Medicine, New York City, NY
- Department of Orthopaedic Surgery, University of Ulm, Ulm, Germany
| | - Jiaqi Zhu
- Biostatistics Core, Hospital for Special Surgery, New York City, NY
| | - Soji Tani
- Department of Orthopaedic Surgery, Hospital for Special Surgery, Weill Cornell Medicine, New York City, NY
- Department of Orthopaedic Surgery, School of Medicine, Showa University Hospital, Tokyo, Japan
| | - Erika Chiapparelli
- Department of Orthopaedic Surgery, Hospital for Special Surgery, Weill Cornell Medicine, New York City, NY
| | - Artine Arzani
- Department of Orthopaedic Surgery, Hospital for Special Surgery, Weill Cornell Medicine, New York City, NY
| | - Jennifer Shue
- Department of Orthopaedic Surgery, Hospital for Special Surgery, Weill Cornell Medicine, New York City, NY
| | | | - Mariana Bendersky
- III Normal Anatomy Department, School of Medicine, University of Buenos Aires
- Intraoperative Monitoring, Department of Pediatric Neurology, Hospital Italiano de Buenos Aires, Buenos Aires, Argentina
| | - William D Zelenty
- Department of Orthopaedic Surgery, Hospital for Special Surgery, Weill Cornell Medicine, New York City, NY
| | - Gbolabo Sokunbi
- Department of Orthopaedic Surgery, Hospital for Special Surgery, Weill Cornell Medicine, New York City, NY
| | - Darren R Lebl
- Department of Orthopaedic Surgery, Hospital for Special Surgery, Weill Cornell Medicine, New York City, NY
| | - Frank P Cammisa
- Department of Orthopaedic Surgery, Hospital for Special Surgery, Weill Cornell Medicine, New York City, NY
| | - Federico P Girardi
- Department of Orthopaedic Surgery, Hospital for Special Surgery, Weill Cornell Medicine, New York City, NY
| | - Carol A Mancuso
- Hospital for Special Surgery, New York City, NY
- Weill Cornell Medical College, New York, NY
| | - Alexander P Hughes
- Department of Orthopaedic Surgery, Hospital for Special Surgery, Weill Cornell Medicine, New York City, NY
| | - Andrew A Sama
- Department of Orthopaedic Surgery, Hospital for Special Surgery, Weill Cornell Medicine, New York City, NY
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Ambrosio L, Mazzuca G, Maguolo A, Russo F, Cannata F, Vadalà G, Maffeis C, Papalia R, Denaro V. The burden of low back pain in children and adolescents with overweight and obesity: from pathophysiology to prevention and treatment strategies. Ther Adv Musculoskelet Dis 2023; 15:1759720X231188831. [PMID: 37694186 PMCID: PMC10492481 DOI: 10.1177/1759720x231188831] [Citation(s) in RCA: 13] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/07/2023] [Accepted: 06/28/2023] [Indexed: 09/12/2023] Open
Abstract
Nonspecific low back pain (LBP) is one of the most common causes of disability, affecting all individuals at least once in their lifetime. Such a condition is also becoming increasingly frequent in the pediatric population, especially in children and adolescents with overweight/obesity. Furthermore, new-onset LBP during adolescence has been demonstrated to be a strong predictor of developing LBP later in life, contributing to poorer outcomes and increasing social and medical costs. Several causes and different mechanisms have been considered for the development of LBP in pediatric individuals affected by obesity. For this reason, planning adequate prevention and treatment strategies, mainly through conservative lifestyle changes, would be crucial to anticipate the negative consequences of persisting LBP in adulthood. The aim of this narrative review was to characterize the relationship between LBP and overweight/obesity in the pediatric population, highlighting epidemiological and pathophysiological aspects. In addition, prevention and treatment approaches will be reviewed considering the need to reduce the burden of LBP on this population. According to our search, LBP was more frequent in children and adolescents with overweight and obesity and has been associated with several anthropometric and lifestyle factors, including lumbar hyperlordosis, sedentary habits, physical inactivity, carrying a heavy schoolbag, low vitamin D levels, psychosocial ill-being, and premature intervertebral disc degeneration. Most of these conditions may be addressed with conservative strategies mainly consisting of dietary adjustments, physical exercise, education programs, and physical therapy.
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Affiliation(s)
- Luca Ambrosio
- Operative Research Unit of Orthopaedic and Trauma Surgery, Fondazione Policlinico Universitario Campus Bio-Medico, Rome, Italy
- Research Unit of Orthopaedic and Trauma Surgery, Department of Medicine and Surgery, Università Campus Bio-Medico di Roma, Rome, Italy
| | - Giorgia Mazzuca
- Section of Pediatric Diabetes and Metabolic Disorders, Department of Surgical Sciences, Dentistry, Pediatrics and Gynaecology, University of Verona, Verona, Italy
| | - Alice Maguolo
- Section of Pediatric Diabetes and Metabolic Disorders, Department of Surgical Sciences, Dentistry, Pediatrics and Gynaecology, University of Verona, Verona, Italy
| | - Fabrizio Russo
- Operative Research Unit of Orthopaedic and Trauma Surgery, Fondazione Policlinico Universitario Campus Bio-Medico, Rome, Italy
- Research Unit of Orthopaedic and Trauma Surgery, Department of Medicine and Surgery, Università Campus Bio-Medico di Roma, Rome, Italy
| | - Francesca Cannata
- Operative Research Unit of Endocrinology and Diabetes, Fondazione Policlinico Universitario Campus Bio-Medico, Rome, Italy
| | - Gianluca Vadalà
- Department of Orthopaedic and Trauma Surgery, Fondazione Policlinico Universitario Campus Bio-Medico, Via Alvaro del Portillo 200, Rome, 00128, Italy
- Research Unit of Orthopaedic and Trauma Surgery, Department of Medicine and Surgery, Università Campus Bio-Medico di Roma, Rome, Italy
| | - Claudio Maffeis
- Section of Pediatric Diabetes and Metabolic Disorders, Department of Surgical Sciences, Dentistry, Pediatrics and Gynaecology, University of Verona, Verona, Italy
| | - Rocco Papalia
- Operative Research Unit of Orthopaedic and Trauma Surgery, Fondazione Policlinico Universitario Campus Bio-Medico, Rome, Italy
- Research Unit of Orthopaedic and Trauma Surgery, Department of Medicine and Surgery, Università Campus Bio-Medico di Roma, Rome, Italy
| | - Vincenzo Denaro
- Operative Research Unit of Orthopaedic and Trauma Surgery, Fondazione Policlinico Universitario Campus Bio-Medico, Rome, Italy
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15
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Chamoro M, de Luca K, Ozbulut O, Oei EHG, Vleggeert-Lankamp CLA, Koes BW, Bierma-Zeinstra SMA, Chiarotto A. Association between clinical findings and the presence of lumbar spine osteoarthritis imaging features: A systematic review. Osteoarthritis Cartilage 2023; 31:1158-1175. [PMID: 37150286 DOI: 10.1016/j.joca.2023.04.014] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/27/2022] [Revised: 04/16/2023] [Accepted: 04/29/2023] [Indexed: 05/09/2023]
Abstract
OBJECTIVE Spinal osteoarthritis is difficult to study and diagnose, partly due to the lack of agreed diagnostic criteria. This systematic review aims to give an overview of the associations between clinical and imaging findings suggestive of spinal osteoarthritis in patients with low back pain to make a step towards agreed diagnostic criteria. DESIGN We searched MEDLINE, Embase, Web of Science, and CINAHL from inception to April 29, 2021 to identify observational studies in adults that assessed the association between selected clinical and imaging findings suggestive of spinal osteoarthritis. Risk of bias was assessed using the Newcastle Ottawa Scale and the quality of evidence was graded using an adaptation of the GRADE approach. RESULTS After screening 7902 studies, 30 met the inclusion criteria. High-quality evidence was found for the longitudinal association between low back pain (LBP) intensity, and both disc space narrowing and osteophytes, as well as for the association between LBP-related physical functioning and lumbar disc degeneration, the presence of spinal morning stiffness and disc space narrowing and for the lack of association between physical functioning and Schmorl's nodes. CONCLUSIONS There is high- and moderate-quality evidence of associations between clinical and imaging findings suggestive of spinal osteoarthritis. However, the majority of the studied outcomes had low or very low-quality of evidence. Furthermore, clinical and methodological heterogeneity was a serious limitation, adding to the need and importance of agreed criteria for spinal osteoarthritis, which should be the scope of future research.
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Affiliation(s)
- Mirna Chamoro
- Department of General Practice, Erasmus MC, University Medical Center, Rotterdam, the Netherlands.
| | - Katie de Luca
- Discipline of Chiropractic, CQ University, Brisbane, Australia.
| | - Omer Ozbulut
- Department of General Practice, Erasmus MC, University Medical Center, Rotterdam, the Netherlands.
| | - Edwin H G Oei
- Department of Radiology & Nuclear Medicine, Erasmus MC, University Medical Center, Rotterdam, the Netherlands.
| | - Carmen L A Vleggeert-Lankamp
- Department of Neurosurgery, Leiden University Medical Center, Leiden, the Netherlands; Department of Neurosurgery, Spaarne Hospital, Haarlem/Hoofddorp, the Netherlands.
| | - Bart W Koes
- Department of General Practice, Erasmus MC, University Medical Center, Rotterdam, the Netherlands; Center for Muscle and Joint Health, University of Southern Denmark, Odense, Denmark.
| | - Sita M A Bierma-Zeinstra
- Department of General Practice, Erasmus MC, University Medical Center, Rotterdam, the Netherlands; Department of Orthopedics, Erasmus MC, University Medical Center, Rotterdam, the Netherlands.
| | - Alessandro Chiarotto
- Department of General Practice, Erasmus MC, University Medical Center, Rotterdam, the Netherlands.
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16
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Keskimölö T, Pernu J, Karppinen J, Niinimäki J, Oura P, Leino T, Honkanen T. Degenerative cervical spine changes among early career fighter pilots: a 5-year follow-up. BMJ Mil Health 2023; 169:291-296. [PMID: 34131064 PMCID: PMC10423485 DOI: 10.1136/bmjmilitary-2021-001848] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/24/2021] [Accepted: 05/29/2021] [Indexed: 11/03/2022]
Abstract
INTRODUCTION Degenerative changes of the cervical spine often cause disability and flight duty limitations among Finnish Air Force (FINAF) fighter pilots. We aimed to study the effect of +Gz exposure on degenerative changes in the cervical spine by comparing cervical MRIs of FINAF fighter pilots and controls. METHODS At baseline, the volunteer study population consisted of 56 20-year-old FINAF male fighter pilots (exposure group) and 56 21-year-old Army and Navy cadets (control group). Both groups underwent MRI of the cervical spine at the baseline and after 5 years. Degenerative changes evaluated using MRI included intervertebral disc (IVD) degeneration (Pfirrmann classification), disc herniations, uncovertebral arthrosis, Schmorl's nodes, Modic changes, spinal canal stenosis, kyphosis and scoliosis. RESULTS The degree of IVD degeneration in the whole cervical spine increased significantly in both populations with no between-group differences. The prevalence of disc herniations also tended to increase in both populations with no difference in the incidence over the follow-up. However, pilots proved to have more disc herniations at the baseline and at the follow-up. There were virtually no between-group differences in other assessed degenerative changes. DISCUSSION We found that IVD degeneration and the prevalence of disc herniations increased at a similar rate for fighter pilots and non-flying military students when all cervical levels were summed up. The lack of difference may be explained by the relatively low cumulative +Gz exposure during the first 5 years of a pilots' career.
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Affiliation(s)
| | - J Pernu
- Faculty of Medicine, University of Oulu, Oulu, Finland
| | - J Karppinen
- Medical Research Center Oulu, Oulu University Hospital, Oulu, Finland
- Finnish Institute of Occupational Health Oulu Regional Office, Oulu, Finland
| | - J Niinimäki
- Faculty of Medicine, University of Oulu, Oulu, Finland
- Medical Research Center Oulu, Oulu University Hospital, Oulu, Finland
| | - P Oura
- Medical Research Center Oulu, Oulu University Hospital, Oulu, Finland
| | - T Leino
- Air Force Command Finland, Tikkakoski, Finland
- Department of Leadership and Military Pedagogy, National Defence University, Helsinki, Finland
| | - T Honkanen
- Aeromedical Centre, Centre for Military Medicine, Finnish Defence Forces, Helsinki, Uusimaa, Finland
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17
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Grahn P, Remes T, Kivisaari R, Suo-Palosaari MH, Arikoski PM, Koskenkorva PKT, Lähteenmäki PM, Lönnqvist TRI, Ojaniemi MK, Sirkiä KH, Sutela AK, Toiviainen-Salo SM, Rantala HMJ, Harila AH, Niinimäki J, Karppinen J, Ahonen M. Early disc degeneration in radiotherapy-treated childhood brain tumor survivors. BMC Musculoskelet Disord 2023; 24:441. [PMID: 37259117 DOI: 10.1186/s12891-023-06509-4] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/28/2022] [Accepted: 05/10/2023] [Indexed: 06/02/2023] Open
Abstract
BACKGROUND Childhood brain tumor (BT) survivors have an increased risk of treatment-related late effects, which can reduce health-related quality of life and increase morbidity. This study aimed to investigate lumbar disc degeneration in magnetic resonance imaging (MRI) in adult survivors of radiotherapy-treated childhood BT compared to age and sex-matched population controls. METHODS In this cross-sectional comparative study, 127 survivors were identified from hospital registries. After a mean follow-up of 20.7 years (range 5-33.1), 67 survivors (mean age 28.4, range 16.2-43.5) were investigated with MRI and compared to 75 sex-matched population-based controls. Evaluated MRI phenotypes included Pfirrmann grading, , intervertebral disc protrusions, extrusions, and high-intensity-zone-lesions (HIZ). Groups were also compared for known risk factors of lumbar intervertebral disc (IVD) degeneration. RESULTS Childhood BT survivors had higher Pfirrmann grades than controls at all lumbar levels (all p < 0.001). Lumbar disc protrusions at L4-5 (p = 0.02) and extrusions at L3-4 (p = 0.04), L4-5 (p = 0.004), and L5-S1 (p = 0.01) were significantly more common in the BT group compared to the control. The survivor cohort also had significantly more HIZ-lesons than the controls (n=13 and n=1, p=0.003). Age at diagnosis was associated with lower degree of IVD degeneration (p < 0.01). Blood pressure correlated with IVD degeneration (P < 0.05). CONCLUSIONS Signs of early disc degeneration related to tumor treatment can be seen in the IVDs of survivors. Disc degeneration was more severe in children treated in adolescence.
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Affiliation(s)
- Petra Grahn
- Department of Pediatric Orthopedics and Traumatology, University of Helsinki and Helsinki University Hospital, Stenbäckinkatu 9, PL 281, 00029, Helsinki, Finland.
| | - Tiina Remes
- Department of Pediatrics and Adolescent Medicine, Oulu University Hospital, and Research Unit of Clinical Medicine, University of Oulu, Helsinki, Finland
- Department of Child Neurology, New Children's Hospital, University of Helsinki, Helsinki University Hospital, Helsinki, Finland
| | - Reetta Kivisaari
- Department of Radiology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
| | - Maria H Suo-Palosaari
- Department of Diagnostic Radiology, Oulu University Hospital and Research Unit of Medical Imaging, Physics, and Technology Medical Research Center Oulu, University of Oulu, Oulu, Finland
| | - Pekka M Arikoski
- Kuopio Pediatric Research Unit, University of Eastern Finland and Kuopio University Hospital, Kuopio, Finland
| | - Päivi K T Koskenkorva
- Department of Clinical Radiology, University of Eastern Finland and Kuopio University Hospital, Kuopio, Finland
| | - Päivi M Lähteenmäki
- Department of Pediatrics and Adolescent Medicine, Turku University Hospital, Turku University, Turku, Finland
| | - Tuula R I Lönnqvist
- Department of Child Neurology, New Children's Hospital, University of Helsinki, Helsinki University Hospital, Helsinki, Finland
| | - Marja K Ojaniemi
- Department of Pediatrics and Adolescent Medicine, Oulu University Hospital, and Research Unit of Clinical Medicine, University of Oulu, Helsinki, Finland
| | - Kirsti H Sirkiä
- Department of Pediatrics and Adolescence, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
| | - Anna K Sutela
- Department of Clinical Radiology, University of Eastern Finland and Kuopio University Hospital, Kuopio, Finland
| | | | - Heikki M J Rantala
- Department of Pediatrics and Adolescent Medicine, Oulu University Hospital, and Research Unit of Clinical Medicine, University of Oulu, Helsinki, Finland
| | - Arja H Harila
- Department of Women's and Children's Health, Uppsala University, Uppsala, Sweden
| | - Jaakko Niinimäki
- Department of Diagnostic Radiology, Oulu University Hospital and Research Unit of Medical Imaging, Physics, and Technology Medical Research Center Oulu, University of Oulu, Oulu, Finland
| | - Jaro Karppinen
- Medical Research Center Oulu, Department of Physical and Rehabilitation Medicine, University of Oulu and Oulu University Hospital, Oulu, Finland
- Finnish Institute of Occupational Health, Oulu, Finland
- Rehabilitation Services of South Karelia Social and Health Care District, Lappeenranta, Finland
| | - Matti Ahonen
- Department of Pediatric Orthopedics and Traumatology, University of Helsinki and Helsinki University Hospital, Stenbäckinkatu 9, PL 281, 00029, Helsinki, Finland
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18
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Yang X, Chen Y, Guo J, Li J, Zhang P, Yang H, Rong K, Zhou T, Fu J, Zhao J. Polydopamine Nanoparticles Targeting Ferroptosis Mitigate Intervertebral Disc Degeneration Via Reactive Oxygen Species Depletion, Iron Ions Chelation, and GPX4 Ubiquitination Suppression. ADVANCED SCIENCE (WEINHEIM, BADEN-WURTTEMBERG, GERMANY) 2023; 10:e2207216. [PMID: 36951540 PMCID: PMC10161035 DOI: 10.1002/advs.202207216] [Citation(s) in RCA: 53] [Impact Index Per Article: 26.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/06/2022] [Revised: 02/08/2023] [Indexed: 05/06/2023]
Abstract
Intervertebral disc degeneration (IVDD)-induced lower back pain (LBP) is a common problem worldwide. The underlying mechanism is partially accredited to ferroptosis, based on sequencing analyses of IVDD patients from the gene expression omnibus (GEO) databases. In this study, it is shown that polydopamine nanoparticles (PDA NPs) inhibit oxidative stress-induced ferroptosis in nucleus pulposus (NP) cells in vitro. PDA NPs scavenge reactive oxygen species (ROS), chelate Fe2+ to mitigate iron overload, and regulate the expression of iron storage proteins such as ferritin heavy chain (FHC), ferritin, and transferrin receptor (TFR). More importantly, PDA NPs co-localize with glutathione peroxidase 4 (GPX4) around the mitochondria and suppress ubiquitin-mediated degradation, which in turn exerts a protective function via the transformation and clearance of phospholipid hydroperoxides. PDA NPs further down-regulate malondialdehyde (MDA) and lipid peroxide (LPO) production; thus, antagonizing ferroptosis in NP cells. Moreover, PDA NPs effectively rescue puncture-induced degeneration in vivo by targeting ferroptosis and inhibiting GPX4 ubiquitination, resulting in the upregulation of antioxidant pathways. The findings offer a new tool to explore the underlying mechanisms and a novel treatment strategy for IVDD-induced LBP.
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Affiliation(s)
- Xiao Yang
- Shanghai Key Laboratory of Orthopedic ImplantsDepartment of OrthopedicsNinth People's HospitalShanghai Jiao Tong University School of Medicine639 Zhizaoju RoadShanghai200011P. R. China
| | - Yan Chen
- Shanghai Key Laboratory of Orthopedic ImplantsDepartment of OrthopedicsNinth People's HospitalShanghai Jiao Tong University School of Medicine639 Zhizaoju RoadShanghai200011P. R. China
| | - Jiadong Guo
- Shanghai Key Laboratory of Orthopedic ImplantsDepartment of OrthopedicsNinth People's HospitalShanghai Jiao Tong University School of Medicine639 Zhizaoju RoadShanghai200011P. R. China
| | - Jiaxin Li
- Department of OrthopedicsThe Second Affiliated Hospital of Harbin Medical University246 Xuefu RoadHarbin150001P. R. China
| | - Pu Zhang
- Shanghai Key Laboratory of Orthopedic ImplantsDepartment of OrthopedicsNinth People's HospitalShanghai Jiao Tong University School of Medicine639 Zhizaoju RoadShanghai200011P. R. China
| | - Huan Yang
- Shanghai Key Laboratory of Orthopedic ImplantsDepartment of OrthopedicsNinth People's HospitalShanghai Jiao Tong University School of Medicine639 Zhizaoju RoadShanghai200011P. R. China
- The Second Clinical Medical College of Yunnan University of Traditional Chinese Medicine1076 Yuhua RoadKunming650500P. R. China
| | - Kewei Rong
- Shanghai Key Laboratory of Orthopedic ImplantsDepartment of OrthopedicsNinth People's HospitalShanghai Jiao Tong University School of Medicine639 Zhizaoju RoadShanghai200011P. R. China
| | - Tangjun Zhou
- Shanghai Key Laboratory of Orthopedic ImplantsDepartment of OrthopedicsNinth People's HospitalShanghai Jiao Tong University School of Medicine639 Zhizaoju RoadShanghai200011P. R. China
| | - Jingke Fu
- Shanghai Key Laboratory of Orthopedic ImplantsDepartment of OrthopedicsNinth People's HospitalShanghai Jiao Tong University School of Medicine639 Zhizaoju RoadShanghai200011P. R. China
| | - Jie Zhao
- Shanghai Key Laboratory of Orthopedic ImplantsDepartment of OrthopedicsNinth People's HospitalShanghai Jiao Tong University School of Medicine639 Zhizaoju RoadShanghai200011P. R. China
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19
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Bonnheim NB, Lazar AA, Kumar A, Akkaya Z, Zhou J, Guo X, O'Neill C, Link TM, Lotz JC, Krug R, Fields AJ. ISSLS Prize in Bioengineering Science 2023: Age- and sex-related differences in lumbar intervertebral disc degeneration between patients with chronic low back pain and asymptomatic controls. EUROPEAN SPINE JOURNAL : OFFICIAL PUBLICATION OF THE EUROPEAN SPINE SOCIETY, THE EUROPEAN SPINAL DEFORMITY SOCIETY, AND THE EUROPEAN SECTION OF THE CERVICAL SPINE RESEARCH SOCIETY 2023; 32:1517-1524. [PMID: 36805320 PMCID: PMC10205694 DOI: 10.1007/s00586-023-07542-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Revised: 10/18/2022] [Accepted: 01/13/2023] [Indexed: 02/20/2023]
Abstract
PURPOSE Clinical management of disc degeneration in patients with chronic low back pain (cLBP) is hampered by the challenge of distinguishing pathologic changes relating to pain from physiologic changes related to aging. The goal of this study was to use imaging biomarkers of disc biochemical composition to distinguish degenerative changes associated with cLBP from normal aging. METHODS T1ρ MRI data were acquired from 133 prospectively enrolled subjects for this observational study (80 cLBP, 53 controls; mean ± SD age = 43.9 ± 13.4 years; 61 females, 72 males). The mean T1ρ relaxation time in the nucleus pulposus (NP-T1ρ; n = 650 discs) was used as a quantitative biomarker of disc biochemical composition. Linear regression was used to assess associations between NP-T1ρ and age, sex, spinal level, and study group, and their interactions. RESULTS NP-T1ρ values were lower in cLBP patients than controls (70.8 ± 22.8 vs. 76.4 ± 22.2 ms, p = 0.009). Group differences were largest at L5-S1 (ΔT1ρcLBP-control = -11.3 ms, p < 0.0001), representing biochemical deterioration typically observed over a 9-12 year period (NP-T1ρ declined by 0.8-1.1 ms per year [95% CI]). Group differences were large in younger patients and diminished with age. Finally, the age-dependence of disc degeneration was stronger in controls than cLBP patients. CONCLUSION Aging effects on the biochemical composition of the L5-S1 disc may involve a relatively uniform set of factors from which many cLBP patients deviate. NP-T1ρ values at L5-S1 may be highly relevant to clinical phenotyping, particularly in younger individuals.
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Affiliation(s)
- Noah B Bonnheim
- Department of Orthopaedic Surgery, University of California, San Francisco, USA
| | - Ann A Lazar
- Department of Epidemiology and Biostatistics, University of California, San Francisco, CA, USA
| | - Anika Kumar
- Department of Orthopaedic Surgery, University of California, San Francisco, USA
| | - Zehra Akkaya
- Department of Radiology and Biomedical Imaging, University of California, San Francisco, CA, USA
| | - Jiamin Zhou
- Department of Orthopaedic Surgery, University of California, San Francisco, USA
| | - Xiaojie Guo
- Department of Orthopaedic Surgery, University of California, San Francisco, USA
| | - Conor O'Neill
- Department of Orthopaedic Surgery, University of California, San Francisco, USA
| | - Thomas M Link
- Department of Radiology and Biomedical Imaging, University of California, San Francisco, CA, USA
| | - Jeffrey C Lotz
- Department of Orthopaedic Surgery, University of California, San Francisco, USA
| | - Roland Krug
- Department of Radiology and Biomedical Imaging, University of California, San Francisco, CA, USA
| | - Aaron J Fields
- Department of Orthopaedic Surgery, University of California, San Francisco, USA.
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20
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Teraguchi M, Hashizume H, Asai Y, Oka H, Nagata K, Ishimoto Y, Iwasaki H, Tsutsui S, Takami M, Tanaka S, Yoshida M, Yoshimura N, Yamada H. Association between modic changes, disc degeneration, and pelvic incidence-lumbar lordosis mismatch in a large population based cohort: the Wakayama spine study. EUROPEAN SPINE JOURNAL : OFFICIAL PUBLICATION OF THE EUROPEAN SPINE SOCIETY, THE EUROPEAN SPINAL DEFORMITY SOCIETY, AND THE EUROPEAN SECTION OF THE CERVICAL SPINE RESEARCH SOCIETY 2023:10.1007/s00586-023-07702-8. [PMID: 37100965 DOI: 10.1007/s00586-023-07702-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/25/2022] [Revised: 04/03/2023] [Accepted: 04/04/2023] [Indexed: 04/28/2023]
Abstract
PURPOSE Sagittal plane alignment is crucial for treating spinal malalignment and low back pain. Pelvic incidence-lumbar lordosis (PI-LL) mismatch is commonly used to evaluate clinical outcomes in patients with sagittal malalignment. The association between PI-LL mismatch and changes surrounding the intervertebral disc is very important to understand the compensatory mechanisms involved. This study aimed to examine the association between PI-LL mismatch and magnetic resonance imaging (MRI) changes surrounding the intervertebral disc in a large population-based cohort. METHODS We evaluated participants from the second Wakayama Spine Study, recruiting the general population aged 20 years or older, irrespective of sex, who were registered residents in one region in 2014. In total, 857 individuals underwent an MRI of the whole spine; however, 43 MRI results were not included due to incomplete or inadequate quality images. PI-LL mismatch was defined as > 11°. We compared the MRI changes, such as Modic change (MC), disc degeneration (DD), and high-intensity zones (HIZ), between PI-LL mismatch and non-PI-LL mismatch groups. Multivariate logistic regression analysis was conducted to determine the association between the MRI changes and PI-LL mismatch with adjustment for age, sex, and body mass index in the lumbar region and at each level. RESULTS A total of 795 participants (243 men, 552 women, mean age 63.5 ± 13.1 years old) were evaluated; 181 were included in the PI-LL mismatch group. MC and DD in the lumbar region were significantly higher in the PI-LL mismatch group. MC in the lumbar region was significantly associated with PI-LL mismatch (odds ratio (OR); 1.81, 95% confidence interval (CI) 1.2-2.7). MC at each level was significantly associated with PI-LL mismatch (OR; 1.7-1.9, 95%CI 1.1-3.2), and DD at L1/2, L3/4, and L4/5 was associated with PI-LL mismatch (OR; 2.0- 2.4. 95%CI 1.2-3.9). CONCLUSION MC and DD were significantly associated with PI-LL mismatch. Therefore, profiling MC may be helpful in improving the targeted treatment of LBP associated with the adult spinal deformity.
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Affiliation(s)
- Masatoshi Teraguchi
- Department of Orthopaedic Surgery, Wakayama Medical University, 811-1 Kimiidera, Wakayama, Wakayama, Japan.
| | - Hiroshi Hashizume
- Department of Orthopaedic Surgery, Wakayama Medical University, 811-1 Kimiidera, Wakayama, Wakayama, Japan
| | - Yoshiki Asai
- Department of Orthopaedic Surgery, Wakayama Medical University, 811-1 Kimiidera, Wakayama, Wakayama, Japan
| | - Hiroyuki Oka
- Department of Medical Research and Management for Musculoskeletal Pain, 22Nd Century Medical and Research Center, Faculty of Medicine, The University of Tokyo, Bunkyo-Ku, Tokyo, Japan
| | - Keiji Nagata
- Department of Orthopaedic Surgery, Wakayama Medical University, 811-1 Kimiidera, Wakayama, Wakayama, Japan
| | - Yuyu Ishimoto
- Department of Orthopaedic Surgery, Wakayama Medical University, 811-1 Kimiidera, Wakayama, Wakayama, Japan
| | - Hiroshi Iwasaki
- Department of Orthopaedic Surgery, Wakayama Medical University, 811-1 Kimiidera, Wakayama, Wakayama, Japan
| | - Shunji Tsutsui
- Department of Orthopaedic Surgery, Wakayama Medical University, 811-1 Kimiidera, Wakayama, Wakayama, Japan
| | - Masanari Takami
- Department of Orthopaedic Surgery, Wakayama Medical University, 811-1 Kimiidera, Wakayama, Wakayama, Japan
| | - Sakae Tanaka
- Department of Orthopaedic Surgery, The University of Tokyo, Bunkyoku, Tokyo, Japan
| | - Munehito Yoshida
- Department of Medical Research and Management for Musculoskeletal Pain, 22Nd Century Medical and Research Center, Faculty of Medicine, The University of Tokyo, Bunkyo-Ku, Tokyo, Japan
- Department of Orthopaedic Surgery, Sumiya Orthopaedic Hospital, Wakayama, Wakayama, Japan
| | - Noriko Yoshimura
- Department of Preventive Medicine for Locomotive Organ Disorders, 22nd Century Medical and Research Center, The University of Tokyo, Bunkyo-Ku, Tokyo, Japan
| | - Hiroshi Yamada
- Department of Orthopaedic Surgery, Wakayama Medical University, 811-1 Kimiidera, Wakayama, Wakayama, Japan
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21
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Mertimo T, Heikkala E, Niinimäki J, Blanco Sequeiros R, Määttä J, Kankaanpää M, Oura P, Karppinen J. The role of co-occurring insomnia and mental distress in the association between lumbar disc degeneration and low back pain related disability. BMC Musculoskelet Disord 2023; 24:293. [PMID: 37060071 PMCID: PMC10103434 DOI: 10.1186/s12891-023-06365-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/01/2022] [Accepted: 03/24/2023] [Indexed: 04/16/2023] Open
Abstract
BACKGROUND Lumbar disc degeneration (LDD) is associated with low back pain (LBP). Although both insomnia and mental distress appear to influence the pain experience, their role in the association between LDD and LBP is uncertain. Our objective was to investigate the role of co-occurring insomnia and mental distress in the association between LDD and LBP-related disability. METHODS A total of 1080 individuals who had experienced LBP during the previous year underwent 1.5-T lumbar magnetic resonance imaging, responded to questionnaires, and participated in a clinical examination at the age of 47. Full data was available for 843 individuals. The presence of LBP and LBP-related disability (numerical rating scale, range 0-10) were assessed using a questionnaire. LDD was assessed by a Pfirrmann-based sum score (range 0-15, higher values indicating higher LDD). The role of insomnia (according to the five-item Athens Insomnia Scale) and mental distress (according to the Hopkins Symptom Check List-25) in the association between the LDD sum score and LBP-related disability was analyzed using linear regression with adjustments for sex, smoking, body mass index, education, leisure-time physical activity, occupational physical exposure, Modic changes, and disc herniations. RESULTS A positive association between LDD and LBP-related disability was observed among those with absence of both mental distress and insomnia (adjusted B = 0.132, 95% CI = 0.028-0.236, p = 0.013), and among those with either isolated mental distress (B = 0.345 CI = 0.039-0.650, p = 0.028) or isolated insomnia (B = 0.207, CI = 0.040-0.373, p = 0.015). However, among individuals with co-occurring insomnia and mental distress, the association was not significant (B = -0.093, CI = -0.346-0.161, p = 0.470). CONCLUSIONS LDD does not associate with LBP-related disability when insomnia and mental distress co-occur. This finding may be useful when planning treatment and rehabilitation that aim to reduce disability among individuals with LDD and LBP. Future prospective research is warranted.
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Affiliation(s)
- Teija Mertimo
- Faculty of Medicine and Health Technology, Tampere University Hospital and University of Tampere, P.O. Box 607, Tampere, FI-33014, Finland.
- Research Unit of Population Health, Faculty of Medicine, University of Oulu, P.O. Box 5000, Oulu, FI- 90014, Finland.
| | - Eveliina Heikkala
- Research Unit of Population Health, Faculty of Medicine, University of Oulu, P.O. Box 5000, Oulu, FI- 90014, Finland
- Medical Research Center Oulu, Oulu University Hospital and University of Oulu, P.O. Box 5000, Oulu, FI-90014, Finland
| | - Jaakko Niinimäki
- Medical Research Center Oulu, Oulu University Hospital and University of Oulu, P.O. Box 5000, Oulu, FI-90014, Finland
- Research Unit of Medical Imaging, Physics and Technology, Faculty of Medicine, University of Oulu, P.O. Box 5000, Oulu, FI-90014, Finland
| | - Roberto Blanco Sequeiros
- Research Unit of Medical Imaging, Physics and Technology, Faculty of Medicine, University of Oulu, P.O. Box 5000, Oulu, FI-90014, Finland
- Department of Radiology, Turku University Hospital, Kiinamyllynkatu 4-8, Turku, FI-20520, Finland
| | - Juhani Määttä
- Medical Research Center Oulu, Oulu University Hospital and University of Oulu, P.O. Box 5000, Oulu, FI-90014, Finland
- Research Unit of Health Sciences and Technology, Faculty of Medicine, University of Oulu, P.O. Box 5000, Oulu, FI-90014, Finland
| | - Markku Kankaanpää
- Department of Rehabilitation and Psychosocial Support, Tampere University Hospital, P.O. Box 2000, Tampere, FI-33521, Finland
| | - Petteri Oura
- Medical Research Center Oulu, Oulu University Hospital and University of Oulu, P.O. Box 5000, Oulu, FI-90014, Finland
- Research Unit of Health Sciences and Technology, Faculty of Medicine, University of Oulu, P.O. Box 5000, Oulu, FI-90014, Finland
| | - Jaro Karppinen
- Medical Research Center Oulu, Oulu University Hospital and University of Oulu, P.O. Box 5000, Oulu, FI-90014, Finland
- Research Unit of Health Sciences and Technology, Faculty of Medicine, University of Oulu, P.O. Box 5000, Oulu, FI-90014, Finland
- Rehabilitation Services of South Karelia Social and Health Care District, Valto Käkelän katu 3, Lappeenranta, FI- 53130, Finland
- Finnish Institute of Occupational Health, Aapistie 1, Oulu, FI-90220, Finland
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22
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Shnayder NA, Ashhotov AV, Trefilova VV, Nurgaliev ZA, Novitsky MA, Vaiman EE, Petrova MM, Nasyrova RF. Cytokine Imbalance as a Biomarker of Intervertebral Disk Degeneration. Int J Mol Sci 2023; 24:ijms24032360. [PMID: 36768679 PMCID: PMC9917299 DOI: 10.3390/ijms24032360] [Citation(s) in RCA: 19] [Impact Index Per Article: 9.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/29/2022] [Revised: 01/09/2023] [Accepted: 01/17/2023] [Indexed: 01/27/2023] Open
Abstract
The intervertebral disk degeneration (IDD) and its associated conditions are an important problem in modern medicine. The onset of IDD may be in childhood and adolescence in patients with a genetic predisposition. IDD progresses with age, leading to spondylosis, spondylarthrosis, intervertebral disk herniation, and spinal stenosis. The purpose of this review is an attempt to summarize the data characterizing the patterns of production of pro-inflammatory and anti-inflammatory cytokines in IDD and to appreciate the prognostic value of cytokine imbalance as its biomarker. This narrative review demonstrates that the problem of evaluating the contribution of pro-inflammatory and anti-inflammatory cytokines to the maintenance or alteration of cytokine balance may be a new key to unlocking the mystery of IDD development and new therapeutic strategies for the treatment of IDD in the setting of acute and chronic inflammation. The presented data support the hypothesis that cytokine imbalance is one of the most important biomarkers of IDD.
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Affiliation(s)
- Natalia A. Shnayder
- Institute of Personalized Psychiatry and Neurology, Shared Core Facilities, V.M. Bekhterev National Medical Research Centre for Psychiatry and Neurology, 192019 Saint Petersburg, Russia
- Shared Core Facilities “Molecular and Cell Technologies”, V.F. Voino-Yasenetsky Krasnoyarsk State Medical University, 660022 Krasnoyarsk, Russia
- Correspondence: (N.A.S.); (R.F.N.); Tel.: +7-(812)-620-0220-7813 (N.A.S. & R.F.N.)
| | - Azamat V. Ashhotov
- Institute of Personalized Psychiatry and Neurology, Shared Core Facilities, V.M. Bekhterev National Medical Research Centre for Psychiatry and Neurology, 192019 Saint Petersburg, Russia
| | | | - Zaitun A. Nurgaliev
- Institute of Personalized Psychiatry and Neurology, Shared Core Facilities, V.M. Bekhterev National Medical Research Centre for Psychiatry and Neurology, 192019 Saint Petersburg, Russia
| | | | - Elena E. Vaiman
- Institute of Personalized Psychiatry and Neurology, Shared Core Facilities, V.M. Bekhterev National Medical Research Centre for Psychiatry and Neurology, 192019 Saint Petersburg, Russia
| | - Marina M. Petrova
- Shared Core Facilities “Molecular and Cell Technologies”, V.F. Voino-Yasenetsky Krasnoyarsk State Medical University, 660022 Krasnoyarsk, Russia
| | - Regina F. Nasyrova
- Institute of Personalized Psychiatry and Neurology, Shared Core Facilities, V.M. Bekhterev National Medical Research Centre for Psychiatry and Neurology, 192019 Saint Petersburg, Russia
- Correspondence: (N.A.S.); (R.F.N.); Tel.: +7-(812)-620-0220-7813 (N.A.S. & R.F.N.)
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23
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El-Hady AO, El Molla SS, Elwan SI, Ibrahim RA. Evaluation of health related quality of life with the use of Oswestry disability index in degenerative discogenic low back pain. EGYPTIAN RHEUMATOLOGY AND REHABILITATION 2023. [DOI: 10.1186/s43166-022-00166-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/19/2023] Open
Abstract
Abstract
Background
Intervertebral disc degeneration (IVD) is a main underlying cause for low back pain (LBP). Oswestry Disability Index (ODI) is a valuable tool used to measure patient’s low back functional outcome. Our aim is to evaluate the relation between clinical assessment of LBP and health related quality of life with the use of ODI and magnetic resonance image (MRI) findings in patients with degenerative prolapsed IVD disease.
Result
There was a significant correlation between Pfirrmann grades and ODI (p < 0.0001) and with type of disc morphology mostly protrusion (p < 0.0001) but insignificant correlation with visual analogue scale (VAS) (p = 0.198) and most of the clinical parameters (p > 0.05). There was a significant correlation between ODI and VAS (p = 0.003). Higher Pfirrmann grades were found at lower lumbosacral levels L4-5 and L5-S1.
Conclusion
Higher Pfirrmann grades correlated with the increased ODI. No association was found between MRI grading in lumbosacral spine with pain intensity and most of the clinical parameters among persons with discogenic LBP. Chronic LBP is widely accepted to be a multifactorial disorder that could not be contained within a single lumbar compartment. Clinician should not depend on MRI findings only in the diagnosis. History from the patient and clinical examination is particularly important to reach the final diagnosis. ODI might be convenient in achieving patient’s confidence and decreasing unnecessary investigations.
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24
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Baker JD, Sayari AJ, Tao Y, Louie PK, Basques BA, Galbusera F, Niemeyer F, Wilke HJ, An HS, Samartzis D. Endplate abnormalities, Modic changes and their relationship to alignment parameters and surgical outcomes in the cervical spine. J Orthop Res 2023; 41:206-214. [PMID: 35398932 DOI: 10.1002/jor.25333] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/28/2022] [Revised: 03/04/2022] [Accepted: 03/22/2022] [Indexed: 02/04/2023]
Abstract
Modic changes (MC) and endplate abnormalities (EA) have been shown to impact preoperative symptoms and outcomes following spinal surgery. However, little is known about how these phenotypes impact cervical alignment. This study aimed to evaluate the impact that these phenotypes have on preoperative, postoperative, and changes in cervical alignment in patients undergoing anterior cervical discectomy and fusion (ACDF). We performed a retrospective study of prospectively collected data of ACDF patients at a single institution. Preoperative magnetic resonance imagings (MRIs) were used to assess for the MC and EA. Patients were subdivided into four groups: MC-only, EA-only, the combined Modic-Endplate-Complex (MEC), and patients without either phenotype. Pre and postoperative MRIs were used to assess alignment parameters. Associations with imaging phenotypes and alignment parameters were assessed, and statistical significance was set at p < 0.5. A total of 512 patients were included, with 84 MC-only patients, 166 EA-only patients, and 71 patients with MEC. Preoperative MC (p = 0.031) and the MEC (p = 0.039) had significantly lower preoperative T1 slope compared to controls. Lower preoperative T1 slope was a risk factor for MC (p = 0.020) and MEC (p = 0.029) and presence of MC (Type II) and the MEC (Type III) was predictive of lower preoperative T1 slope. There were no differences in postoperative alignment measures or patient reported outcome measures. MC and endplate pathologies such as the MEC appear to be associated with worse cervical alignment at baseline relative to patients without these phenotypes. Poor alignment may be an adaptive response to these degenerative findings or may be a risk factor for their development.
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Affiliation(s)
- James D Baker
- Department of Orthopaedic Surgery, Rush University Medical Center, Chicago, Illinois, USA.,International Spine Research and Innovation Initiative (ISRII), Rush University Medical Center, Chicago, Illinois, USA
| | - Arash J Sayari
- Department of Orthopaedic Surgery, Rush University Medical Center, Chicago, Illinois, USA.,International Spine Research and Innovation Initiative (ISRII), Rush University Medical Center, Chicago, Illinois, USA
| | - Youping Tao
- Institute of Orthopaedic Research and Biomechanics, Centre for Trauma Research Ulm, Ulm University Medical Centre, Ulm, Germany
| | - Philip K Louie
- Department of Neurosurgery, Neuroscience Institute, Virginia Mason Franciscan Health, Seattle, Washington State, USA
| | - Bryce A Basques
- Department of Orthopaedic Surgery, Rush University Medical Center, Chicago, Illinois, USA.,International Spine Research and Innovation Initiative (ISRII), Rush University Medical Center, Chicago, Illinois, USA
| | | | - Frank Niemeyer
- Institute of Orthopaedic Research and Biomechanics, Centre for Trauma Research Ulm, Ulm University Medical Centre, Ulm, Germany
| | - Hans-Joachim Wilke
- Institute of Orthopaedic Research and Biomechanics, Centre for Trauma Research Ulm, Ulm University Medical Centre, Ulm, Germany
| | - Howard S An
- Department of Orthopaedic Surgery, Rush University Medical Center, Chicago, Illinois, USA.,International Spine Research and Innovation Initiative (ISRII), Rush University Medical Center, Chicago, Illinois, USA
| | - Dino Samartzis
- Department of Orthopaedic Surgery, Rush University Medical Center, Chicago, Illinois, USA.,International Spine Research and Innovation Initiative (ISRII), Rush University Medical Center, Chicago, Illinois, USA
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25
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Wen P, Zheng B, Zhang B, Ma T, Hao L, Zhang Y. The role of ageing and oxidative stress in intervertebral disc degeneration. Front Mol Biosci 2022; 9:1052878. [PMID: 36419928 PMCID: PMC9676652 DOI: 10.3389/fmolb.2022.1052878] [Citation(s) in RCA: 28] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/24/2022] [Accepted: 10/25/2022] [Indexed: 10/10/2023] Open
Abstract
Intervertebral disc degeneration (IDD) is the primary cause of intervertebral disc (IVD) disease. With the increased ageing of society, an increasing number of patients are plagued by intervertebral disc disease. Ageing not only accelerates the decreased vitality and functional loss of intervertebral disc cells but also increases intracellular oxidative stress. Moreover, the speed of intervertebral disc ageing is also linked to high levels of reactive oxygen species (ROS) production. Not only is the production of ROS increased in ageing intervertebral disc cells, but antioxidant levels in degenerative intervertebral discs also decrease. In addition to the intervertebral disc, the structural components of the intervertebral disc matrix are vulnerable to oxidative damage. After chronic mitochondrial dysfunction, ROS can be produced in large quantities, while autophagy can eliminate these impaired mitochondria to reduce the production of ROS. Oxidative stress has a marked impact on the occurrence of IDD. In the future, IDD treatment is aiming to improve oxidative stress by regulating the redox balance in intervertebral disc cells. In summary, ageing and oxidative stress promote the degeneration of IVD, but further basic and clinical trials are needed to determine how to treat oxidative stress. At present, although there are many in-depth studies on the relationship between oxidative stress and degeneration of intervertebral disc cells, the specific mechanism has not been elucidated. In this paper, the main causes of intervertebral disc diseases are studied and summarized, and the impact of oxidative stress on intervertebral disc degeneration is studied.
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Affiliation(s)
- Pengfei Wen
- Department of Joint Surgery, Honghui Hospital, Xi’an Jiaotong University, Xi’an, Shaanxi, China
| | - Bolong Zheng
- Department of Spine Surgery, Honghui Hospital, Xi’an Jiaotong University, Xi’an, Shaanxi, China
| | - Binfei Zhang
- Department of Joint Surgery, Honghui Hospital, Xi’an Jiaotong University, Xi’an, Shaanxi, China
| | - Tao Ma
- Department of Joint Surgery, Honghui Hospital, Xi’an Jiaotong University, Xi’an, Shaanxi, China
| | - Linjie Hao
- Department of Joint Surgery, Honghui Hospital, Xi’an Jiaotong University, Xi’an, Shaanxi, China
| | - Yumin Zhang
- Department of Joint Surgery, Honghui Hospital, Xi’an Jiaotong University, Xi’an, Shaanxi, China
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Lund T, Schlenzka D, Lohman M, Ristolainen L, Kautiainen H, Klemetti E, Österman K. The intervertebral disc during growth: Signal intensity changes on magnetic resonance imaging and their relevance to low back pain. PLoS One 2022; 17:e0275315. [PMID: 36194584 PMCID: PMC9531821 DOI: 10.1371/journal.pone.0275315] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2022] [Accepted: 09/12/2022] [Indexed: 11/16/2022] Open
Abstract
Life-time prevalence of low back pain (LBP) in children and adolescents varies from 7% to 72%. Disc changes on magnetic resonance imaging (MRI) have been reported in up to 44% of children with earliest observations around pre-puberty. In this longitudinal cohort study, our objective was to determine the natural history of disc changes from childhood to early adulthood, and the possible association of these changes to LBP. Healthy 8-year-old schoolchildren were recruited for this longitudinal study consisting of a semi-structured interview, a clinical examination, and an MRI investigation at the age of 8-9 (Y8), 11-12 (Y12) and 18-19 (Y19) years. The interview inquired about LBP without trauma. T2-weighted sagittal MRI of the lumbar spine was acquired. Life-long prevalence of LBP was determined, and the disc signal intensity (SI) at the three lowest lumbar levels was assessed both visually using the Schneiderman classification (Bright-Speckled-Dark), and digitally using the disc to cerebrospinal fluid -SI ratio. Possible associations between SI changes and LBP were analyzed. Ninety-four of 208 eligible children were included at Y8 in 1994, 13 and 23 participants were lost to follow-up at Y12 and Y19, respectively. Prevalence of LBP increased after the pubertal growth spurt reaching 54% at Y19. On MRI, 18%, 10% and 38% of participants had disc SI changes at Y8, Y12 and Y19, respectively. No significant associations between self-reported LBP and either qualitative or quantitative disc SI changes were observed at any age. Life-time prevalence of LBP reached 54% by early adulthood. Disc SI changes on MRI traditionally labeled as degenerative were seen earlier than previously reported. Changes in disc SI were not associated with the presence of LBP in childhood, adolescence or early adulthood.
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Affiliation(s)
- Teija Lund
- Department of Orthopaedics and Traumatology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
- * E-mail:
| | | | - Martina Lohman
- Department of Radiology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
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Mechanisms and functions of long noncoding RNAs in intervertebral disc degeneration. Pathol Res Pract 2022; 235:153959. [DOI: 10.1016/j.prp.2022.153959] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/12/2022] [Revised: 05/04/2022] [Accepted: 05/25/2022] [Indexed: 01/17/2023]
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Yang X, Li B, Tian H, Cheng X, Zhou T, Zhao J. Curcumenol Mitigates the Inflammation and Ameliorates the Catabolism Status of the Intervertebral Discs In Vivo and In Vitro via Inhibiting the TNFα/NFκB Pathway. Front Pharmacol 2022; 13:905966. [PMID: 35795557 PMCID: PMC9252100 DOI: 10.3389/fphar.2022.905966] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2022] [Accepted: 05/11/2022] [Indexed: 11/25/2022] Open
Abstract
Low back pain (LBP) caused by intervertebral disc degeneration (IVDD) is accredited to the release of inflammatory cytokines followed by biomechanical and structural deterioration. In our study, we used a plant-derived medicine, curcumenol, to treat IVDD. A cell viability test was carried out to evaluate the possibility of using curcumenol. RNA-seq was used to determine relative pathways involved with curcumenol addition. Using TNFα as a trigger of inflammation, the activation of the NF-κB signaling pathway and expression of the MMP family were determined by qPCR and western blotting. Nucleus pulposus (NP) cells and the rats’ primary NP cells were cultured. The catabolism status was evaluated by an ex vivo model. A lumbar instability mouse model was carried out to show the effects of curcumenol in vivo. In general, RNA-seq revealed that multiple signaling pathways changed with curcumenol addition, especially the TNFα/NF-κB pathway. So, the NP cells and primary NP cells were induced to suffer inflammation with the activated TNFα/NF-κB signaling pathway and increased expression of the MMP family, such as MMP3, MMP9, and MMP13, which would be mitigated by curcumenol. Owing to the protective effects of curcumenol, the height loss and osteophyte formation of the disc could be prevented in the lumbar instability mouse model in vivo.
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Affiliation(s)
| | | | | | | | | | - Jie Zhao
- *Correspondence: Tangjun Zhou, ; Jie Zhao,
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Wang DK, Zheng HL, Zhou WS, Duan ZW, Jiang SD, Li B, Zheng XF, Jiang LS. Mitochondrial Dysfunction in Oxidative Stress-Mediated Intervertebral Disc Degeneration. Orthop Surg 2022; 14:1569-1582. [PMID: 35673928 PMCID: PMC9363752 DOI: 10.1111/os.13302] [Citation(s) in RCA: 50] [Impact Index Per Article: 16.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/25/2021] [Revised: 04/08/2022] [Accepted: 04/11/2022] [Indexed: 11/29/2022] Open
Abstract
Intervertebral disc degeneration (IVDD) is the most common contributor to low back pain (LBP). Recent studies have found that oxidative stress and reactive oxygen species (ROS) play an important role in IVDD. As a by‐product of aerobic respiration, ROS is mainly produced in the mitochondria by the electron transport chain and other mitochondrial located proteins. With the excessive accumulation of ROS, mitochondria are also the primary target of ROS attack in disc cells. A disrupted balance between intracellular ROS production and antioxidant capacity will lead to oxidative stress, which is the key contributor to cell apoptosis, cell senescence, excessive autophagy, and mitochondrial dysfunction. As the pivotal ingredient of oxidative stress, mitochondrial dysfunction manifests as imbalanced mitochondrial dynamics and dysregulated mitophagy. Mitochondria can alter their own dynamics through the process of fusion and fission, so that disabled mitochondria can be separated from the mitochondrial pool. Moreover, mitophagy participates by clearing these dysfunctional mitochondria. Abnormality in any of these processes either increases the production or decreases the clearance of ROS, leading to a vicious cycle that results in the death of intervertebral disc cells in large quantities, combined with degradation of the extracellular matrix and overproduction of matrix metalloproteinase. In this review, we explain the changes in mitochondrial morphology and function during oxidative stress‐mediated IVDD and highlight the important role of mitochondria in this process. Eventually, we summarize the IVDD therapeutic strategies targeting mitochondrial dysfunction based on current understanding of the role of oxidative stress in IVDD.
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Affiliation(s)
- Dian-Kai Wang
- Department of Spine Centre, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Huo-Liang Zheng
- Department of Spine Centre, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Wen-Sheng Zhou
- Department of Spine Centre, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Zheng-Wei Duan
- Department of Orthopedics, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Sheng-Dan Jiang
- Department of Spine Centre, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Bo Li
- Department of Spine Centre, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Xin-Feng Zheng
- Department of Spine Centre, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Lei-Sheng Jiang
- Department of Spine Centre, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
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Lukecha KR, Geoffrey E, Gonzaga MA, Sam B. Magnetic resonance imaging findings among young adults with low back pain at Nsambya hospital. BMC Med Imaging 2022; 22:108. [PMID: 35659200 PMCID: PMC9166491 DOI: 10.1186/s12880-022-00830-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/16/2021] [Accepted: 05/16/2022] [Indexed: 11/10/2022] Open
Abstract
Abstract
Background
Studies on MRI findings among patients with LBP have been conducted; especially among adolescents and young adult population in developed countries. However, MRI lumbar spine evaluation findings in young adult patients with low back pain in Uganda is not known. The purpose of this study was to determine the MRI findings and their correlation to clinical features in young adult patients with low back pain in Nsambya hospital.
Methods
This was a descriptive cross sectional study. One hundred and fifty-seven patients with low back pain in the 18–39 year age group underwent MRI lumbar spine evaluation. The MRI changes in the lumbar spine and correlation to clinical features were determined. Correlation was assessed by Pearson chi square tests (Fisher’s exact test) and p values reported at 0.05 level of significance.
Results
Of the 157 patients 129 (82.2%) had severe pain, whereas ninety (57.3%) had pain that had lasted more than 10 weeks. Sixty-five (41.4%) patients were found to have MRI evidence of disc desiccation, majority (61%) of whom had multiple level disease, mostly involving the lowest 2 disc levels. Facet joint arthropathy (47.8%), marginal osteophyte (31.8%) and disc contour irregularity [disc bulge] (31.2%) were other common MRI features seen. There was an association between duration of pain and limb weakness, and development of marginal osteophytes. There was also association between clinical presentation and disc bulge.
Conclusions
The MRI finding of disc degeneration among young adult patients with LBP is higher than reported. Age and pain distribution are predictors of developing disc desiccation.
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Mertimo T, Karppinen J, Niinimäki J, Blanco R, Määttä J, Kankaanpää M, Oura P. Association of lumbar disc degeneration with low back pain in middle age in the Northern Finland Birth Cohort 1966. BMC Musculoskelet Disord 2022; 23:359. [PMID: 35428226 PMCID: PMC9011971 DOI: 10.1186/s12891-022-05302-z] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/10/2022] [Accepted: 03/30/2022] [Indexed: 11/10/2022] Open
Abstract
Abstract
Background
Although it has been suggested that lumbar disc degeneration (LDD) is a significant risk factor for low back pain (LBP), its role remains uncertain. Our objective was to clarify the association between LDD and LBP and whether mental distress modifies the association.
Methods
Participants of a birth cohort underwent 1.5-T lumbar magnetic resonance imaging at the age of 47. The association between the sum score of LDD (Pfirrmann classification, range 0–15) and LBP (categorized into “no pain”, “mild-to-moderate pain”, “bothersome-and-frequent pain”) was assessed using logistic regression analysis, with sex, smoking, body mass index, physical activity, occupational exposure, education, and presence of Modic changes and disc herniations as confounders. The modifying role of mental distress (according to the Hopkins Symptom Check List-25 [HSCL-25], the Beck Depression Inventory and the Generalized Anxiety Disorder Scale) in the association was analyzed using linear regression.
Results
Of the study population (n = 1505), 15.2% had bothersome and frequent LBP, and 29.0% had no LBP. A higher LDD sum score increased the odds of belonging to the “mild-to-moderate pain” category (adjusted OR corresponding to an increase of one point in the LDD sum score 1.11, 95% CI 1.04–1.18, P = 0.003) and the “bothersome-and-frequent pain” category (adjusted OR 1.20, 95% CI 1.10–1.31, P < 0.001), relative to the “no pain” category. Mental distress significantly modified the association between LDD and LBP, as a linear positive association was consistently observed among individuals without mental distress according to HSCL-25 (adjusted B 0.16, 95% CI 0.07–0.26, P < 0.001), but not among individuals with higher mental distress.
Conclusions
LDD was significantly associated with both mild-to-moderate and bothersome-and-frequent LBP. However, the co-occurrence of mental distress diminished the association between LDD and LBP bothersomeness. Our results strongly suggest that mental symptoms affect the pain experience.
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Zhang Z, Huang Y, Xu N, Wang J, Yao T, Xu Y, Qiao D, Gao J, Shen S, Ma J. PLK1 Mitigates Intervertebral Disc Degeneration by Delaying Senescence of Nucleus Pulposus Cells. Front Cell Dev Biol 2022; 10:819262. [PMID: 35372354 PMCID: PMC8964438 DOI: 10.3389/fcell.2022.819262] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/21/2021] [Accepted: 02/11/2022] [Indexed: 01/07/2023] Open
Abstract
Intervertebral disc degeneration (IVDD) is the primary cause of low back pain; however, the molecular mechanisms involved in the pathogenesis of IVDD are not fully understood. Polo-like kinase 1 (PLK1) plays numerous roles in the cell cycle, including in cell proliferation and senescence. To investigate the involvement of PLK1 in IVDD, we used patient tissues and an animal model of IVDD. Samples were analyzed via immunoblotting, quantitative real-time polymerase chain reaction (qPCR), immunofluorescence, and immunohistochemistry. Our results demonstrated that PLK1 expression was decreased in nucleus pulposus cells (NPCs) of degenerative IVDs. The inhibition of PLK1 kinase activity in normal NPCs increased the expression of p53 protein, inhibited cell proliferation, and induced senescence. Our results suggest that PLK1 regulates the degeneration of the IVD through p53, revealing the function and mechanism of PLK1 in IVDD and providing a theoretical basis and experimental evidence for the potential treatment of low back pain.
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Affiliation(s)
- Zhenlei Zhang
- Department of Orthopaedic Surgery, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China.,Key Laboratory of Musculoskeletal System Degeneration and Regeneration Translational Research of Zhejiang University Zhejiang Province, Hangzhou, China
| | - Yizhen Huang
- Department of Orthopaedic Surgery, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China.,Key Laboratory of Musculoskeletal System Degeneration and Regeneration Translational Research of Zhejiang University Zhejiang Province, Hangzhou, China
| | - Nizhen Xu
- Department of Head and Neck Surgery, Institute of Micro-Invasive Surgery of Zhejiang University, Sir Run Run Shaw Hospital, Medical School, Hangzhou, China
| | - Jianle Wang
- Department of Orthopaedic Surgery, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China.,Key Laboratory of Musculoskeletal System Degeneration and Regeneration Translational Research of Zhejiang University Zhejiang Province, Hangzhou, China
| | - Teng Yao
- Department of Orthopaedic Surgery, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China.,Key Laboratory of Musculoskeletal System Degeneration and Regeneration Translational Research of Zhejiang University Zhejiang Province, Hangzhou, China
| | - Yining Xu
- Key Laboratory of Musculoskeletal System Degeneration and Regeneration Translational Research of Zhejiang University Zhejiang Province, Hangzhou, China.,Shaoxing University School of Medicine, Shaoxing, China
| | - Di Qiao
- Key Laboratory of Musculoskeletal System Degeneration and Regeneration Translational Research of Zhejiang University Zhejiang Province, Hangzhou, China.,Shaoxing University School of Medicine, Shaoxing, China
| | - Jun Gao
- Department of Orthopaedic Surgery, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China.,Key Laboratory of Musculoskeletal System Degeneration and Regeneration Translational Research of Zhejiang University Zhejiang Province, Hangzhou, China
| | - Shuying Shen
- Department of Orthopaedic Surgery, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China.,Key Laboratory of Musculoskeletal System Degeneration and Regeneration Translational Research of Zhejiang University Zhejiang Province, Hangzhou, China
| | - Jianjun Ma
- Department of Orthopaedic Surgery, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China.,Key Laboratory of Musculoskeletal System Degeneration and Regeneration Translational Research of Zhejiang University Zhejiang Province, Hangzhou, China.,Shaoxing University School of Medicine, Shaoxing, China
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Widjaja G, Jalil AT, Budi HS, Abdelbasset WK, Efendi S, Suksatan W, Rita RS, Satria AP, Aravindhan S, Saleh MM, Shalaby MN, Yumashev AV. Mesenchymal stromal/stem cells and their exosomes application in the treatment of intervertebral disc disease: A promising frontier. Int Immunopharmacol 2022. [DOI: https://doi.org/10.1016/j.intimp.2022.108537] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]
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34
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Widjaja G, Jalil AT, Budi HS, Abdelbasset WK, Efendi S, Suksatan W, Rita RS, Satria AP, Aravindhan S, Saleh MM, Shalaby MN, Yumashev AV. Mesenchymal stromal/stem cells and their exosomes application in the treatment of intervertebral disc disease: A promising frontier. Int Immunopharmacol 2022; 105:108537. [PMID: 35101851 DOI: 10.1016/j.intimp.2022.108537] [Citation(s) in RCA: 38] [Impact Index Per Article: 12.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/26/2021] [Revised: 01/01/2022] [Accepted: 01/07/2022] [Indexed: 02/07/2023]
Abstract
Today, the application of mesenchymal stromal/stem cells (MSCs) and their exosomes to treat degenerative diseases has received attention. Due to the characteristics of these cells, such as self-renewability, differentiative and immunomodulatory effects, their use in laboratory and clinical studies shows promising results. However, the allogeneic transplantation problems of MSCs limit the use of these cells in the clinic. Scientists propose the application of exosomes to use from the therapeutic effect of MSCs and overcome their defects. These vesicles change the target cell behaviour and transcription profile by transferring various cargo such as proteins, mi-RNAs, and lipids. One of the degenerative tissue diseases in which MSCs and their exosomes are used in their treatment is intervertebral disc disease (IDD). Different factors such as genetics, nutrition, ageing, and environmental factors play a significant role in the onset and progression of this disease. These factors affect the cellular and molecular properties of the disc, leading to tissue destruction. Nucleus pulposus cells (NPCs) are among the most important cells involved in the pathogenesis of disc degeneration. MSCs exert their therapeutic effects by differentiating, reducing apoptosis, increasing proliferation, and decreasing senescence in NPCs. In addition, the use of MSCs and their exosomes also affects the annulus fibrosus and cartilaginous endplate cells in disc tissue and prevents disc degeneration progression.
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Affiliation(s)
- Gunawan Widjaja
- Postgraduate Study, Universitas Krisnadwipayana, Bekasi, Indonesia; Faculty of Public Health, Universitas Indonesia, Depok, Indonesia
| | - Abduladheem Turki Jalil
- Faculty of Biology and Ecology, Yanka Kupala State University of Grodno, 230023 Grodno, Belarus; College of Technical Engineering, The Islamic University, Najaf, Iraq; Department of Dentistry, Kut University College, Kut, Wasit 52001, Iraq
| | - Hendrik Setia Budi
- Department of Oral Biology, Faculty of Dental Medicine, Universitas Airlangga, Surabaya 60132, Indonesia.
| | - Walid Kamal Abdelbasset
- Department of Health and Rehabilitation Sciences, College of Applied Medical Sciences, Prince Sattam bin Abdulaziz University, Al Kharj, Saudi Arabia; Department of Physical Therapy, Kasr Al-Aini Hospital, Cairo University, Giza, Egypt
| | - Syahril Efendi
- Fasilkom-TI, Universitas Sumatera Utara, Medan, Indonesia.
| | - Wanich Suksatan
- Faculty of Nursing, HRH Princess Chulabhorn College of Medical Science, Chulabhorn Royal Academy, Bangkok 10210, Thailand
| | - Rauza Sukma Rita
- Department of Biochemistry, Faculty of Medicine, Universitas Andalas, Indonesia
| | - Andri Praja Satria
- Faculty of Nursing, Universitas Muhammadiyah Kalimantan Timur, Samarinda 75124, Indonesia
| | - Surendar Aravindhan
- Department of Pharmacology, Saveetha Dental College and Hospital, Saveetha Institute of Medical and Technical Sciences, Chennai, India
| | - Marwan Mahmood Saleh
- Department of Biophysics, College of Applied Sciences, University Of Anbar, Iraq
| | - Mohammed Nader Shalaby
- Biological Sciences and Sports Health Department, Faculty of Physical Education, Suez Canal University, Egypt
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Sneath RJS, Khan A, Hutchinson C. An Objective Assessment of Lumbar Spine Degeneration/Ageing Seen on MRI Using An Ensemble Method-A Novel Approach to Lumbar MRI Reporting. Spine (Phila Pa 1976) 2022; 47:E187-E195. [PMID: 34224512 DOI: 10.1097/brs.0000000000004159] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/01/2023]
Abstract
STUDY DESIGN Retrospective, randomized, radiographic study assessing age-related changes (ARCs) on lumbar magnetic resonance imaging (MRI) using an ensemble method. OBJECTIVES This study proposed to develop a novel reporting method to calculate a predicted "age estimate" for the ARC seen on lumbar MRI. SUMMARY OF BACKGROUND DATA Lumbar MRI reports include pathological findings but usually not the prevalence data of common findings which has been shown to decrease the need for narcotics in the management of non-specific lower back pain (NSLBP). Comparing the normal age estimation for lumbar spine degenerative changes/ARC on MRI and comparing this to the patient's real age may improve patient outcome in the management of NSLBP. METHODS A total of 60 lumbar MRI were taken from patients aged between 0 and 100 years. Lumbar MRI features reported as associated with age on review of the literature were measured on each MRI and statistically evaluated for correlation with age. Factors found to be associated were then entered into an ensemble model consisting of several machine learning techniques. The resulting ensemble model was then tested to predict age for a further 10 random lumbar MRI scans. One further lumbar MRI was then assessed for observer variability. RESULTS Features that correlated with age were disc signal intensity, the appearance of paravertebral and psoas muscle, disc height, facet joint size, ligamentum flavum thickness, Schmorl nodes, Modic changes, vertebral osteophytes, and high-intensity zones. With the ensemble model, 80% of estimated spinal age were within 11 years of the subjects' physical age. CONCLUSION It would appear that the intervertebral discs, and many other structures that are subjected to loading in and around the lumbar spine change their lumbar MRI appearance in a predictable way with increasing age. ARC on lumbar MRI can be assessed to predict an "expected age" for the subject.Level of Evidence: 2.
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Chan LY, Chang CC, Lai PL, Maeda T, Hsu HC, Lin CY, Kuo SJ. Cre/LoxP Genetic Recombination Sustains Cartilage Anabolic Factor Expression in Hyaluronan Encapsulated MSCs Alleviates Intervertebral Disc Degeneration. Biomedicines 2022; 10:biomedicines10030555. [PMID: 35327357 PMCID: PMC8945655 DOI: 10.3390/biomedicines10030555] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/10/2022] [Revised: 02/14/2022] [Accepted: 02/24/2022] [Indexed: 02/04/2023] Open
Abstract
(1) Background: Inexplicable low back and neck pain frequently results from spinal disc degeneration with an imbalanced intervertebral disc (IVD) cell homeostasis. We hypothesize that introducing MSC expressing a sustained cartilage-anabolic factor in the IVD may stimulate the mucoid materials secreted from the IVD cells, promote the MSC’s chondrogenesis and maintain the hydration content providing mechanical strength to decelerate the disc degeneration progression; (2) Methods: This study expressed a cartilage-anabolic factor runx1 by a baculoviral vector (BV) transduced MSCs through a Cre/LoxP gene editing and recombination system for sustained recombinant runx1 transcription factor production. The Cre/LoxP BV modified MSCs were encapsulated by hyaluronan hydrogel, due to its’ vital composition in ECM of a healthy disc and transplanted to a punctured coccygeal disc in rats through micro-injection, followed by X-ray radiography and histological analysis at the 4- and 12-weeks post-transplantation; (3) Results: Data reveals the Cre/LoxP BV system-mediated long-termed runx1 gene expression, possessing good biosafety characteristics in the in vitro cell transduction and in vivo MSCs transplantation, and maintained superior hydration content in the disc than that of mock transduced MSCs; (4) Conclusions: This proof-of-concept study fulfills the need of implanting therapeutic cells accompanied with microinjection in the disc, such as a discography and paves a road to manufacture composite hyaluronan, such as peptide modified hyaluronan as an MSC carrier for IVD regeneration in the future study.
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Affiliation(s)
- Long-Yi Chan
- Institute of New Drug Development, College of Medicine, China Medical University, Taichung 40402, Taiwan; (L.-Y.C.); (C.-C.C.)
| | - Cheng-Chung Chang
- Institute of New Drug Development, College of Medicine, China Medical University, Taichung 40402, Taiwan; (L.-Y.C.); (C.-C.C.)
| | - Po-Liang Lai
- Department of Orthopedic Surgery, Chang Gung Memorial Hospital, Tau-Yuan 333, Taiwan;
| | - Tomoji Maeda
- Tsuzuki Institute for Traditional Medicine, College of Pharmacy, China Medical University, Taichung 40402, Taiwan;
- Department of Pharmaceutical Sciences, Nihon Pharmaceutical University, Kitaadachi-gun, Saitama 362-0806, Japan
| | - Horng-Chaung Hsu
- School of Medicine, China Medical University, Taichung 40402, Taiwan;
- Department of Orthopedic Surgery, China Medical University Hospital, Taichung 40447, Taiwan
| | - Chin-Yu Lin
- Institute of New Drug Development, College of Medicine, China Medical University, Taichung 40402, Taiwan; (L.-Y.C.); (C.-C.C.)
- Tsuzuki Institute for Traditional Medicine, College of Pharmacy, China Medical University, Taichung 40402, Taiwan;
- Master Program for Biomedical Engineering, Collage of Biomedical Engineering, China Medical University, Taichung 40402, Taiwan
- Correspondence: (C.-Y.L.); (S.-J.K.); Tel.: +886-4-2205-3366 (ext. 8108) (C.-Y.L.); +886-4-2205-2121 (ext. 5052) (S.-J.K.)
| | - Shu-Jui Kuo
- School of Medicine, China Medical University, Taichung 40402, Taiwan;
- Department of Orthopedic Surgery, China Medical University Hospital, Taichung 40447, Taiwan
- Correspondence: (C.-Y.L.); (S.-J.K.); Tel.: +886-4-2205-3366 (ext. 8108) (C.-Y.L.); +886-4-2205-2121 (ext. 5052) (S.-J.K.)
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Wu ZL, Chen YJ, Zhang GZ, Xie QQ, Wang KP, Yang X, Liu TC, Wang ZQ, Zhao GH, Zhang HH. SKI knockdown suppresses apoptosis and extracellular matrix degradation of nucleus pulposus cells via inhibition of the Wnt/β-catenin pathway and ameliorates disc degeneration. Apoptosis 2022; 27:133-148. [PMID: 35147801 DOI: 10.1007/s10495-022-01707-2] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 12/28/2021] [Indexed: 01/18/2023]
Abstract
This study aimed to determine the effects of SKI on interleukin (IL)-1β-induced apoptosis of nucleus pulposus (NP) cells, intervertebral disc degeneration (IDD), and the Wnt signaling pathway. NP tissue specimens of different Pfirrmann grades (II-V) were collected from patients with different grades of IDD. Real-time polymerase chain reaction and western blotting were used to compare SKI mRNA and protein expression in NP tissues from patients. Using the IL-1β-induced IDD model, NP cells were infected with lentivirus-coated si-SKI to downregulate the expression of SKI and treated with LiCl to evaluate the involvement of the Wnt/β-catenin signaling pathway. Western blotting, immunofluorescence, and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining were used to detect NP cell apoptosis, extracellular matrix (ECM) metabolism, and related protein expression changes in the Wnt/β-catenin signaling pathway. To investigate the role of SKI in vivo, a rat IDD model was established by needle puncture of the intervertebral disc. Rats were injected with lentivirus-coated si-SKI and evaluated by magnetic resonance imaging (MRI), and hematoxylin and eosin (HE) and safranin O staining. SKI expression positively correlated with the severity of human IDD. In the IL-1β-induced NP cell degeneration model, SKI expression increased significantly and reached a peak at 24 h. SKI knockdown protected against IL-1β-induced NP cell apoptosis and ECM degradation. LiCl treatment reversed the protective effects of si-SKI on NP cells. Furthermore, lentivirus-coated si-SKI injection partially reversed the NP tissue damage in the IDD model in vivo. SKI knockdown reduced NP cell apoptosis and ECM degradation by inhibiting the Wnt/β-catenin signaling pathway, ultimately protecting against IDD. Therefore, SKI may be an effective target for IDD treatment.
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Affiliation(s)
- Zuo-Long Wu
- Department of Orthopaedics, Second Hospital of Lanzhou University, Gansu, 730000, China
- Key Laboratory of Orthopaedics Disease of Gansu Province, Gansu, 730000, China
- Lanzhou University, Lanzhou, 730000, Gansu, China
| | - Ya-Jun Chen
- Lanzhou University, Lanzhou, 730000, Gansu, China
- Lanzhou Maternal and Child Health Hospital, Lanzhou, 730000, Gansu, China
| | - Guang-Zhi Zhang
- Department of Orthopaedics, Second Hospital of Lanzhou University, Gansu, 730000, China
- Key Laboratory of Orthopaedics Disease of Gansu Province, Gansu, 730000, China
- Lanzhou University, Lanzhou, 730000, Gansu, China
| | - Qi-Qi Xie
- Department of Orthopaedics, Second Hospital of Lanzhou University, Gansu, 730000, China
- Key Laboratory of Orthopaedics Disease of Gansu Province, Gansu, 730000, China
- Lanzhou University, Lanzhou, 730000, Gansu, China
| | - Ke-Ping Wang
- Department of Orthopaedics, Second Hospital of Lanzhou University, Gansu, 730000, China
- Key Laboratory of Orthopaedics Disease of Gansu Province, Gansu, 730000, China
- Lanzhou University, Lanzhou, 730000, Gansu, China
| | - Xin Yang
- Department of Orthopaedics, Second Hospital of Lanzhou University, Gansu, 730000, China
- Key Laboratory of Orthopaedics Disease of Gansu Province, Gansu, 730000, China
- Lanzhou University, Lanzhou, 730000, Gansu, China
| | - Tai-Cong Liu
- Department of Orthopaedics, Second Hospital of Lanzhou University, Gansu, 730000, China
- Key Laboratory of Orthopaedics Disease of Gansu Province, Gansu, 730000, China
- Lanzhou University, Lanzhou, 730000, Gansu, China
| | - Zhi-Qiang Wang
- Department of Orthopaedics, Second Hospital of Lanzhou University, Gansu, 730000, China
- Key Laboratory of Orthopaedics Disease of Gansu Province, Gansu, 730000, China
- Lanzhou University, Lanzhou, 730000, Gansu, China
| | - Guang-Hai Zhao
- Department of Orthopaedics, Second Hospital of Lanzhou University, Gansu, 730000, China
- Key Laboratory of Orthopaedics Disease of Gansu Province, Gansu, 730000, China
- Lanzhou University, Lanzhou, 730000, Gansu, China
| | - Hai-Hong Zhang
- Department of Orthopaedics, Second Hospital of Lanzhou University, Gansu, 730000, China.
- Key Laboratory of Orthopaedics Disease of Gansu Province, Gansu, 730000, China.
- Lanzhou University, Lanzhou, 730000, Gansu, China.
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Smith A, Hancock M, O'Hanlon S, Krieser M, O'Sullivan P, Cicuttini F, Straker L, Adler B, Wang Y, Karppinen J, Samartzis D, Beales D, Coenen P, Kent P. The Association Between Different Trajectories of Low Back Pain and Degenerative Imaging Findings in Young Adult Participants Within The Raine Study. Spine (Phila Pa 1976) 2022; 47:269-276. [PMID: 34269758 DOI: 10.1097/brs.0000000000004171] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/01/2023]
Abstract
STUDY DESIGN Case-control study. OBJECTIVE Investigate the association between lumbar spine magnetic resonance imaging (MRI) findings and 5-year trajectories of low back pain (LBP) in young Australian adults. SUMMARY OF BACKGROUND DATA The association between lumbar spine imaging findings and LBP remains unclear due to important limitations of previous research, such as a lack of clearly defined LBP phenotypes and inadequate controlling for age, which may substantially affect the association. METHODS Seventy-eight "case" participants with a previously identified "consistent high disabling LBP" trajectory from age 17 to 22 years and 78 "control" participants from a trajectory with consistently low LBP over the same time period, matched for sex, body mass index, physical activity levels, and work physical demands, were identified from Gen2 Raine Study participants. At age 27, participants underwent a standardized lumbar MRI scan, from which 14 specific MRI phenotypes were identified. Primary analyses used unconditional logistic regression, adjusting for covariates used in the matching process, to investigate the relationship between presence of each imaging finding and being a case or control. Secondary analyses explored those relationships based on the number of spinal levels with each MRI finding. RESULTS The odds for being a case compared with a control were higher in those with disc degeneration (Pfirrmann grade ≥ 3; OR = 3.21, 95% CI: 1.60-6.44; P = 0.001) or those with a herniation (OR = 1.90, 95% CI: 0.96-3.74; P - 0.065). We also found that the association became substantially stronger when either disc degeneration or herniation was present at two or more spinal levels (OR = 5.56, 95% CI: 1.97-15.70; P = 0.001, and OR = 5.85, 95% CI: 1.54-22.25; P = 0.009, respectively). The other investigated MRI findings were not associated with greater odds of being a case. CONCLUSION Lumbar disc degeneration and herniation may be important contributors to disabling LBP in young adults. Further investigation of their potential prognostic and causal roles is indicated.Level of Evidence: 4.
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Affiliation(s)
- Anne Smith
- Curtin School of Allied Health, Curtin University, Perth, Australia
| | - Mark Hancock
- Faculty of Medicine, Health and Human Sciences, Macquarie University, Sydney, Australia
| | - Susan O'Hanlon
- Envision Medical Imaging, Perth, Australia
- Fiona Stanley Hospital, Perth, Australia
| | - Michael Krieser
- Envision Medical Imaging, Perth, Australia
- Fiona Stanley Hospital, Perth, Australia
| | - Peter O'Sullivan
- Curtin School of Allied Health, Curtin University, Perth, Australia
| | - Flavia Cicuttini
- School of Public Health and Preventive Medicine, Monash University, Melbourne, Australia
| | - Leon Straker
- Curtin School of Allied Health, Curtin University, Perth, Australia
| | | | - YuanYuan Wang
- School of Public Health and Preventive Medicine, Monash University, Melbourne, Australia
| | - Jaro Karppinen
- Medical Research Center Oulu, Oulu University Hospital and University of Oulu, Oulu, Finland
- Rehabilitation Services of South Karelia Social and Health Care District, Lappeenranta, Finland
| | - Dino Samartzis
- Department of Orthopaedic Surgery, RUSH University, Chicago, IL
| | - Darren Beales
- Curtin School of Allied Health, Curtin University, Perth, Australia
| | - Pieter Coenen
- Amsterdam UMC, Vrije Universiteit, Department of Public and Occupational Health, Amsterdam Public Health Research Institute, Amsterdam, The Netherlands
| | - Peter Kent
- Curtin School of Allied Health, Curtin University, Perth, Australia
- Center for Muscle and Joint Health, University of Southern Denmark, Odense, Denmark
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39
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Baker JD, Sayari AJ, Harada GK, Tao Y, Louie PK, Basques BA, Galbusera F, Niemeyer F, Wilke HJ, An HS, Samartzis D. The Modic-endplate-complex phenotype in cervical spine patients: Association with symptoms and outcomes. J Orthop Res 2022; 40:449-459. [PMID: 33749924 DOI: 10.1002/jor.25042] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/23/2020] [Revised: 03/15/2021] [Accepted: 03/19/2021] [Indexed: 02/04/2023]
Abstract
This study describes a novel, combined Modic changes (MC) and structural endplate abnormality phenotype of the cervical spine, which we have termed the Modic-Endplate-Complex (MEC), and its association with preoperative symptoms and outcomes in anterior cervical discectomy and fusion (ACDF) patients. This was a retrospective study of prospectively collected data at a single institution. Preoperative cervical magnetic resonance imagings were used to assess the presence of MC and endplate abnormalities. Patients were divided into four groups: MC-only, endplate abnormality-only, the MEC and controls. The MEC was defined as the presence of both a MC and endplate abnormality in the cervical spine. Phenotypes were further stratified by location and compared to controls. Associations with patient-reported outcome measures were assessed using regression controlling for baseline characteristics. A total of 628 patients were included, with 84 MC-only, 166 endplate abnormality-only, and 187 MEC patients. Both MC (p < 0.001) and endplate abnormalities (p < 0.001) were independently associated with one another. MC at the adjacent level (p = 0.018), endplate abnormalities (regardless of location) (p = 0.001), and the MEC within the fusion segment (p = 0.027) were all associated with higher Neck Disability Index scores. Both MC within the fusion segment (p = 0.008) and endplate abnormalities within the fusion segment (p = 0.017) associated with lower Veteran's Rand 12-item scores. MC and structural endplate abnormalities commonly manifest concomitantly in patients indicated for ACDF for degenerative pathology. Patients with the endplate pathology, including the MEC phenotype, reported significantly higher levels of postoperative disability following ACDF. These findings add valuable data to the prognostic assessment of degenerative cervical spine patients.
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Affiliation(s)
- James D Baker
- Department of Orthopaedic Surgery, Rush University Medical Center, Chicago, Illinois, USA.,Department of Orthopaedic Surgery, International Spine Research and Innovation Initiative (ISRII), Rush University Medical Center, Chicago, Illinois, USA
| | - Arash J Sayari
- Department of Orthopaedic Surgery, Rush University Medical Center, Chicago, Illinois, USA.,Department of Orthopaedic Surgery, International Spine Research and Innovation Initiative (ISRII), Rush University Medical Center, Chicago, Illinois, USA
| | - Garrett K Harada
- Department of Orthopaedic Surgery, Rush University Medical Center, Chicago, Illinois, USA.,Department of Orthopaedic Surgery, International Spine Research and Innovation Initiative (ISRII), Rush University Medical Center, Chicago, Illinois, USA
| | - Youping Tao
- Institute of Orthopaedic Research and Biomechanics, Centre for Trauma Research Ulm, Ulm University Medical Centre, Ulm, Germany
| | - Philip K Louie
- Department of Neurosurgery, Neuroscience Institute, Virginia Mason Medical Center, Seattle, Washington, USA
| | - Bryce A Basques
- Department of Orthopaedic Surgery, Rush University Medical Center, Chicago, Illinois, USA.,Department of Orthopaedic Surgery, International Spine Research and Innovation Initiative (ISRII), Rush University Medical Center, Chicago, Illinois, USA
| | - Fabio Galbusera
- Department of Orthopaedic Surgery, IRCCS Istituto Ortopedico Galeazzi, Milan, Italy
| | - Frank Niemeyer
- Institute of Orthopaedic Research and Biomechanics, Centre for Trauma Research Ulm, Ulm University Medical Centre, Ulm, Germany
| | - Hans-Joachim Wilke
- Institute of Orthopaedic Research and Biomechanics, Centre for Trauma Research Ulm, Ulm University Medical Centre, Ulm, Germany
| | - Howard S An
- Department of Orthopaedic Surgery, Rush University Medical Center, Chicago, Illinois, USA.,Department of Orthopaedic Surgery, International Spine Research and Innovation Initiative (ISRII), Rush University Medical Center, Chicago, Illinois, USA
| | - Dino Samartzis
- Department of Orthopaedic Surgery, Rush University Medical Center, Chicago, Illinois, USA.,Department of Orthopaedic Surgery, International Spine Research and Innovation Initiative (ISRII), Rush University Medical Center, Chicago, Illinois, USA
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Chang CC, Tsou HK, Chang HH, Chan LY, Zhuo GY, Maeda T, Lin CY. Runx1 Messenger RNA Delivered by Polyplex Nanomicelles Alleviate Spinal Disc Hydration Loss in a Rat Disc Degeneration Model. Int J Mol Sci 2022; 23:565. [PMID: 35008997 PMCID: PMC8745749 DOI: 10.3390/ijms23010565] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/17/2021] [Revised: 12/18/2021] [Accepted: 01/03/2022] [Indexed: 02/04/2023] Open
Abstract
Vertebral disc degenerative disease (DDD) affects millions of people worldwide and is a critical factor leading to low back and neck pain and consequent disability. Currently, no strategy has addressed curing DDD from fundamental aspects, because the pathological mechanism leading to DDD is still controversial. One possible mechanism points to the homeostatic status of extracellular matrix (ECM) anabolism, and catabolism in the disc may play a vital role in the disease's progression. If the damaged disc receives an abundant amount of cartilage, anabolic factors may stimulate the residual cells in the damaged disc to secrete the ECM and mitigate the degeneration process. To examine this hypothesis, a cartilage anabolic factor, Runx1, was expressed by mRNA through a sophisticated polyamine-based PEG-polyplex nanomicelle delivery system in the damaged disc in a rat model. The mRNA medicine and polyamine carrier have favorable safety characteristics and biocompatibility for regenerative medicine. The endocytosis of mRNA-loaded polyplex nanomicelles in vitro, mRNA delivery efficacy, hydration content, disc shrinkage, and ECM in the disc in vivo were also examined. The data revealed that the mRNA-loaded polyplex nanomicelle was promptly engulfed by cellular late endosome, then spread into the cytosol homogeneously at a rate of less than 20 min post-administration of the mRNA medicine. The mRNA expression persisted for at least 6-days post-injection in vivo. Furthermore, the Runx1 mRNA delivered by polyplex nanomicelles increased hydration content by ≈43% in the punctured disc at 4-weeks post-injection (wpi) compared with naked Runx1 mRNA administration. Meanwhile, the disc space and ECM production were also significantly ameliorated in the polyplex nanomicelle group. This study demonstrated that anabolic factor administration by polyplex nanomicelle-protected mRNA medicine, such as Runx1, plays a key role in alleviating the progress of DDD, which is an imbalance scenario of disc metabolism. This platform could be further developed as a promising strategy applied to regenerative medicine.
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Affiliation(s)
- Cheng-Chung Chang
- Institute of New Drug Development, College of Medicine, China Medical University, Taichung 40402, Taiwan; (C.-C.C.); (H.-H.C.); (L.Y.C.); (G.-Y.Z.)
| | - Hsi-Kai Tsou
- Functional Neurosurgery Division, Neurological Institute, Taichung Veterans General Hospital, Taichung 40705, Taiwan;
- Department of Rehabilitation, Jen-Teh Junior College of Medicine, Nursing and Management, Miaoli County 35664, Taiwan
- College of Medicine, National Chung Hsing University, Taichung 40227, Taiwan
- College of Health, National Taichung University of Science and Technology, Taichung 40401, Taiwan
| | - Hsu-Hsin Chang
- Institute of New Drug Development, College of Medicine, China Medical University, Taichung 40402, Taiwan; (C.-C.C.); (H.-H.C.); (L.Y.C.); (G.-Y.Z.)
| | - Long Yi Chan
- Institute of New Drug Development, College of Medicine, China Medical University, Taichung 40402, Taiwan; (C.-C.C.); (H.-H.C.); (L.Y.C.); (G.-Y.Z.)
| | - Guan-Yu Zhuo
- Institute of New Drug Development, College of Medicine, China Medical University, Taichung 40402, Taiwan; (C.-C.C.); (H.-H.C.); (L.Y.C.); (G.-Y.Z.)
| | - Tomoji Maeda
- Tsuzuki Institute for Traditional Medicine, College of Pharmacy, China Medical University, Taichung 40402, Taiwan;
- Department of Pharmaceutical Sciences, Nihon Pharmaceutical University, Kitaadachi-gun, Saitama 362-0806, Japan
| | - Chin-Yu Lin
- Institute of New Drug Development, College of Medicine, China Medical University, Taichung 40402, Taiwan; (C.-C.C.); (H.-H.C.); (L.Y.C.); (G.-Y.Z.)
- Tsuzuki Institute for Traditional Medicine, College of Pharmacy, China Medical University, Taichung 40402, Taiwan;
- Master Program for Biomedical Engineering, Collage of Biomedical Engineering, China Medical University, Taichung 40402, Taiwan
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41
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A new immunometabolic perspective of intervertebral disc degeneration. Nat Rev Rheumatol 2022; 18:47-60. [PMID: 34845360 DOI: 10.1038/s41584-021-00713-z] [Citation(s) in RCA: 239] [Impact Index Per Article: 79.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 10/20/2021] [Indexed: 12/12/2022]
Abstract
Intervertebral disc (IVD) degeneration is a common finding on spine imaging that increases in prevalence with age. IVD degeneration is a frequent cause of low back pain, which is a leading cause of disability. The process of IVD degeneration consists of gradual structural change accompanied by severe alterations in metabolic homeostasis. IVD degeneration, like osteoarthritis, is a common comorbidity in patients with obesity and type 2 diabetes mellitus, two metabolic syndrome pathological conditions in which adipokines are important promoters of low-grade inflammation, extracellular matrix degradation and fibrosis. Impairment in white adipose tissue function, due to the abnormal fat accumulation in obesity, is characterized by increased production of specific pro-inflammatory proteins such as adipokines by white adipose tissue and of cytokines such as TNF by immune cells of the stromal compartment. Investigations into the immunometabolic alterations in obesity and type 2 diabetes mellitus and their interconnections with IVD degeneration provide insights into how adipokines might affect the pathogenesis of IVD degeneration and impair IVD function and repair. Toll-like receptor-mediated signalling has also been implicated as a promoter of the inflammatory response in the metabolic alterations associated with IVD and is thus thought to have a role in IVD degeneration. Pathological starvation, obesity and adipokine dysregulation can result in immunometabolic alterations, which could be targeted for the development of new therapeutics.
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42
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Beales D, Kent P, Birkrem MB, Man Chow C, Li LK, Tan RLJ, Kendell M, Straker L, O'Sullivan P, Smith A. Only one fifth of young Australian adults have beliefs about medical imaging for low back pain that align with current evidence: A cross-sectional study. Musculoskelet Sci Pract 2021; 56:102460. [PMID: 34547611 DOI: 10.1016/j.msksp.2021.102460] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/02/2021] [Revised: 07/31/2021] [Accepted: 09/09/2021] [Indexed: 10/20/2022]
Abstract
BACKGROUND Patients' perceptions/expectations may be a factor behind medical imaging referral rates. Few studies have investigated the beliefs that might drive expectations of medical imaging. OBJECTIVES This study examined whether beliefs of young Australian adults with and without impactful low back pain (LBP) concerning medical scans for LBP align with current evidence. It also investigated if these beliefs were associated with clinical factors (history of impactful LBP, history of previous medical scans, LBP-related disability and the presence of leg pain) or sociodemographic factors (sex, education, income). DESIGN Cross-sectional observational study. METHODS 78 participants from the Raine Study with a history of impactful LBP and 85 participants with no history of impactful LBP completed a study-specific questionnaire with five statements concerning beliefs about medical imaging for LBP. All statements were not aligned with current evidence about the use of medical imaging in LBP management. RESULTS Only 15-21% (n = 24-34) of the participants held beliefs that were aligned with current evidence. Participants with a university education had slightly more aligned beliefs compared to those whose highest education was completing secondary school. There was no difference in the beliefs of participants based on their history of impactful LBP, or other clinical or sociodemographic factors. CONCLUSION As beliefs are likely to drive care-seeking behavior, it is notable that most participants' views about the role of medical imaging for LBP were not aligned with current evidence. Therefore, this suggests a need for community education, especially for those with lower education.
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Affiliation(s)
- Darren Beales
- Curtin EnAble Institute and Curtin School of Allied Health, Curtin University, Perth, Australia.
| | - Peter Kent
- Curtin EnAble Institute and Curtin School of Allied Health, Curtin University, Perth, Australia; Center for Muscle and Joint Health, University of Southern Denmark, Odense, Denmark.
| | - Magnus B Birkrem
- Curtin EnAble Institute and Curtin School of Allied Health, Curtin University, Perth, Australia.
| | - Cheuk Man Chow
- Curtin EnAble Institute and Curtin School of Allied Health, Curtin University, Perth, Australia.
| | - Lap Kiu Li
- Curtin EnAble Institute and Curtin School of Allied Health, Curtin University, Perth, Australia.
| | - Rui Ling Joleen Tan
- Curtin EnAble Institute and Curtin School of Allied Health, Curtin University, Perth, Australia.
| | - Michelle Kendell
- Curtin EnAble Institute and Curtin School of Allied Health, Curtin University, Perth, Australia.
| | - Leon Straker
- Curtin EnAble Institute and Curtin School of Allied Health, Curtin University, Perth, Australia.
| | - Peter O'Sullivan
- Curtin EnAble Institute and Curtin School of Allied Health, Curtin University, Perth, Australia.
| | - Anne Smith
- Curtin EnAble Institute and Curtin School of Allied Health, Curtin University, Perth, Australia.
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Lagerbäck T, Kastrati G, Möller H, Jensen K, Skorpil M, Gerdhem P. MRI Characteristics at a Mean of Thirteen Years After Lumbar Disc Herniation Surgery in Adolescents: A Case-Control Study. JB JS Open Access 2021; 6:JBJSOA-D-21-00081. [PMID: 34841186 PMCID: PMC8613359 DOI: 10.2106/jbjs.oa.21.00081] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/26/2022] Open
Abstract
The purpose of this study was to describe the prevalence of lumbar spine degeneration in adult individuals who had undergone lumbar disc herniation surgery during adolescence.
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Affiliation(s)
- Tobias Lagerbäck
- Department of Clinical Science, Intervention and Technology, Division of Orthopedics and Biotechnology, Karolinska Institutet, Stockholm, Sweden.,Department of Reconstructive Orthopedics, Karolinska University Hospital, Stockholm, Sweden
| | - Gránit Kastrati
- Department of Clinical Neuroscience, Division of Neuro, Karolinska Institutet, Stockholm, Sweden
| | - Hans Möller
- Department of Clinical Science, Intervention and Technology, Division of Orthopedics and Biotechnology, Karolinska Institutet, Stockholm, Sweden.,Center for Spine Surgery in Stockholm, Södra Fiskartorpsvägen, Stockholm, Sweden
| | - Karin Jensen
- Department of Clinical Neuroscience, Division of Neuro, Karolinska Institutet, Stockholm, Sweden
| | - Mikael Skorpil
- Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.,Department of Neuroradiology, Karolinska University Hospital, Stockholm, Sweden
| | - Paul Gerdhem
- Department of Clinical Science, Intervention and Technology, Division of Orthopedics and Biotechnology, Karolinska Institutet, Stockholm, Sweden.,Department of Reconstructive Orthopedics, Karolinska University Hospital, Stockholm, Sweden
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Ketola JHJ, Inkinen SI, Karppinen J, Niinimäki J, Tervonen O, Nieminen MT. T 2 -weighted magnetic resonance imaging texture as predictor of low back pain: A texture analysis-based classification pipeline to symptomatic and asymptomatic cases. J Orthop Res 2021; 39:2428-2438. [PMID: 33368707 DOI: 10.1002/jor.24973] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/23/2020] [Revised: 11/20/2020] [Accepted: 12/21/2020] [Indexed: 02/04/2023]
Abstract
Low back pain is a very common symptom and the leading cause of disability throughout the world. Several degenerative imaging findings seen on magnetic resonance imaging are associated with low back pain but none of them is specific for the presence of low back pain as abnormal findings are prevalent among asymptomatic subjects as well. The purpose of this population-based study was to investigate if more specific magnetic resonance imaging predictors of low back pain could be found via texture analysis and machine learning. We used this methodology to classify T2 -weighted magnetic resonance images from the Northern Finland Birth Cohort 1966 data to symptomatic and asymptomatic groups. Lumbar spine magnetic resonance imaging was performed using a fast spin-echo sequence at 1.5 T. Texture analysis pipeline consisting of textural feature extraction, principal component analysis, and logistic regression classifier was applied to the data to classify them into symptomatic (clinically relevant pain with frequency ≥30 days and intensity ≥6/10) and asymptomatic (frequency ≤7 days, intensity ≤3/10, and no previous pain episodes in the follow-up period) groups. Best classification results were observed applying texture analysis to the two lowest intervertebral discs (L4-L5 and L5-S1), with accuracy of 83%, specificity of 83%, sensitivity of 82%, negative predictive value of 94%, precision of 56%, and receiver operating characteristic area-under-curve of 0.91. To conclude, textural features from T2 -weighted magnetic resonance images can be applied in low back pain classification.
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Affiliation(s)
- Juuso H J Ketola
- Research Unit of Medical Imaging, Physics and Technology, University of Oulu, Oulu, Finland
| | - Satu I Inkinen
- Research Unit of Medical Imaging, Physics and Technology, University of Oulu, Oulu, Finland
| | - Jaro Karppinen
- Medical Research Center Oulu, Oulu University Hospital and University of Oulu, Oulu, Finland.,Department of Physical and Rehabilitation Medicine, Rehabilitation Services of South Karelia Social and Health Care District, Lappeenranta, Finland.,Department of Occupational Health, Finnish Institute of Occupational Health, Oulu, Finland
| | - Jaakko Niinimäki
- Research Unit of Medical Imaging, Physics and Technology, University of Oulu, Oulu, Finland.,Medical Research Center Oulu, Oulu University Hospital and University of Oulu, Oulu, Finland.,Department of Diagnostic Radiology, Oulu University Hospital, Oulu, Finland
| | - Osmo Tervonen
- Research Unit of Medical Imaging, Physics and Technology, University of Oulu, Oulu, Finland.,Medical Research Center Oulu, Oulu University Hospital and University of Oulu, Oulu, Finland.,Department of Diagnostic Radiology, Oulu University Hospital, Oulu, Finland
| | - Miika T Nieminen
- Research Unit of Medical Imaging, Physics and Technology, University of Oulu, Oulu, Finland.,Medical Research Center Oulu, Oulu University Hospital and University of Oulu, Oulu, Finland.,Department of Diagnostic Radiology, Oulu University Hospital, Oulu, Finland
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45
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Singh R, Kumar P, Wadhwani J, Yadav RK, Khanna M, Kaur S. A comparative study to evaluate disc degeneration on magnetic resonance imaging in patients with chronic low back pain and asymptomatic individuals. JOURNAL OF ORTHOPAEDICS, TRAUMA AND REHABILITATION 2021. [DOI: 10.1177/22104917211039522] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022] Open
Abstract
Objectives The present study aimed to investigate the association of disc degeneration with low back pain and the effect of ageing on disc degeneration in low back pain versus asymptomatic individuals. Methodology A total of 50 patients with chronic low back pain (Group A) were compared to 25 healthy controls (Group B). Both the groups were subjected to magnetic resonance imaging of the lumbar spine and the disc degeneration was measured by the Pfirrmann grading system. The study group (Group A) was further sub-grouped into A1 (lumbar spondylosis, n = 11), A2 (mechanical back pain, n = –13) and A3 (lumbar disc herniation, n = 26). Results There was a statistically significant difference in degeneration at the L4-L5 ( p = 0.001) and L5-S1 disc levels ( p = 0.001) between the two groups and contiguous disc involvement was more in low back pain patients. The subgroups of group A showed no statistically significant difference. Age showed a strong positive correlation ( r > 0.5) at all the lumbar levels (except at the L5-S1, r = 0.487) with Pfirrmann grading in Group A ( p = 0.001). There was a weak positive correlation ( r = 0.414) between age and Pfirrmann grade in the controls ( p = 0.04) at the L4-L5 level only. Conclusions Significantly higher Pfirrmann grading on magnetic resonance imaging was found at the L4-5 and L5-S1 levels in symptomatic patients suggesting higher involvement of these levels. Progressive disc degeneration is seen with ageing but in patients with low back pain, it is significantly accelerated.
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Affiliation(s)
- Roop Singh
- Department of Orthopaedic Surgery, Paraplegia & Rehabilitation, Pt. B.D. Sharma PGIMS, India
| | | | - Jitendra Wadhwani
- Department of Orthopaedic Surgery, Paraplegia & Rehabilitation, Pt. B.D. Sharma PGIMS, India
| | - Rohtas K Yadav
- Department of Radiodiagnosis and Imaging, Pt. B.D. Sharma PGIMS, India
| | - Mohit Khanna
- Department of Orthopaedic Surgery, Paraplegia & Rehabilitation, Pt. B.D. Sharma PGIMS, India
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Zhou Z, Wang Y, Liu H, Wang L, Liu Z, Yuan H, Liu L, Guo M, Wang D. PBN protects NP cells from AAPH-induced degenerative changes by inhibiting the ERK1/2 pathway. Connect Tissue Res 2021; 62:359-368. [PMID: 32183547 DOI: 10.1080/03008207.2020.1743697] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/03/2023]
Abstract
Aim: Intervertebral disc (IVD) degeneration (IDD) is one of the main causes for spinal degenerative diseases, such as disk herniation, spinal canal stenosis, and spinal deformities. Growing evidence has highlighted the contribution of oxidative stress in pathogenesis of IDD, and antioxidant treatment is thus considered to be a promising therapeutic strategy for IDD. The aim of this study was to investigate whether N-tert-butyl-α-phenylnitrone (PBN), a free radical scavenger, could attenuate the pathological changes of IDD by alleviating oxidative stress.Materials and Methods: Nucleus pulposus (NP) cells were isolated from rabbit lumbar disks. MTT assay, real-time PCR and western blotting were employed to evaluate the effects of PBN on oxidative damages induced by 2,2'-azobis (2-amidinopropane) dihydrochloride (AAPH) in NP cells.Results: AAPH induced oxidative stress and the subsequent degenerative changes in NP cells via the ERK/MAPK pathway. On the contrary, the oxidative stress induced by AAPH was significantly ameliorated by PBN. Moreover, PBN also attenuated AAPH-induced expression of matrix degradation proteases and apoptosis. PBN suppresses AAPH-induced activation of ERK/MAPK pathway, which may be the underlying mechanism for the protective effects of PBN.Conclusions: Our study for the first time identified a novel role and mechanism for PBN in protecting the IVD against oxidative stress, matrix catabolism and apoptosis, which may have implications for its further application in combating IVD degenerative diseases.Abbreviations: AAPH: 2,2'-azobis(2-methylpropanimidamidine) dihydrochloride; ADAMTS: a disintegrin and metalloproteinase with thrombospondin motifs; AF: annulus fibrosus; CEP: cartilage endplate; DCF: 2'7'-dichlorofluorescein; IDD: intervertebral disc degeneration; IVD: intervertebral disc; LPS: lipopolysaccharide; MMP: matrix metalloproteinase; MTT: methyl-thiazolyl-tetrazolium; NP: nucleus pulposus; PBN: N-tert-butyl-alfa-phenylnitrone; PGs: proteoglycans; ROS: reactive oxygen species; SDS: sodium dodecyl sulfate.
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Affiliation(s)
- Zhenggang Zhou
- Medical College, Qingdao University, Qingdao, Shandong, China
| | - Yini Wang
- Department of Emergency Medicine, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, China
| | - Haifei Liu
- Qingdao Municipal Hospital, Department of Spine Surgery Center, The 3rd Clinical College of Qingdao University, Qingdao, Shandong, China
| | - Lu Wang
- Department of Exercise Physiology, Beijing Sport University, Beijing, China
| | - Zonghan Liu
- Department of Exercise Physiology, Beijing Sport University, Beijing, China
| | - Huimei Yuan
- Department of Exercise Physiology, Beijing Sport University, Beijing, China
| | - Lantao Liu
- Qingdao Municipal Hospital, Department of Spine Surgery Center, The 3rd Clinical College of Qingdao University, Qingdao, Shandong, China
| | - Mingbo Guo
- Department of Osteology, Sunshine Union Hospital, Weifang, Shandong, China
| | - Dechun Wang
- Qingdao Municipal Hospital, Department of Spine Surgery Center, The 3rd Clinical College of Qingdao University, Qingdao, Shandong, China
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47
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Le Maitre CL, Dahia CL, Giers M, Illien‐Junger S, Cicione C, Samartzis D, Vadala G, Fields A, Lotz J. Development of a standardized histopathology scoring system for human intervertebral disc degeneration: an Orthopaedic Research Society Spine Section Initiative. JOR Spine 2021; 4:e1167. [PMID: 34337340 PMCID: PMC8313169 DOI: 10.1002/jsp2.1167] [Citation(s) in RCA: 33] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/26/2021] [Revised: 05/25/2021] [Accepted: 06/07/2021] [Indexed: 12/29/2022] Open
Abstract
BACKGROUND Histopathological analysis of intervertebral disc (IVD) tissues is a critical domain of back pain research. Identification, description, and classification of attributes that distinguish abnormal tissues form a basis for probing disease mechanisms and conceiving novel therapies. Unfortunately, lack of standardized methods and nomenclature can limit comparisons of results across studies and prevent organizing information into a clear representation of the hierarchical, spatial, and temporal patterns of IVD degeneration. Thus, the following Orthopaedic Research Society (ORS) Spine Section Initiative aimed to develop a standardized histopathology scoring scheme for human IVD degeneration. METHODS Guided by a working group of experts, this prospective process entailed a series of stages that consisted of reviewing and assessing past grading schemes, surveying IVD researchers globally on current practice and recommendations for a new grading system, utilizing expert opinion a taxonomy of histological grading was developed, and validation performed. RESULTS A standardized taxonomy was developed, which showed excellent intra-rater reliability for scoring nucleus pulposus (NP), annulus fibrosus (AF), and cartilaginous end plate (CEP) regions (interclass correlation [ICC] > .89). The ability to reliably detect subtle changes varied by IVD region, being poorest in the NP (ICC: .89-.95) where changes at the cellular level were important, vs the AF (ICC: .93-.98), CEP (ICC: .97-.98), and boney end plate (ICC: .96-.99) where matrix and structural changes varied more dramatically with degeneration. CONCLUSIONS The proposed grading system incorporates more comprehensive descriptions of degenerative features for all the IVD sub-tissues than prior criteria. While there was excellent reliability, our results reinforce the need for improved training, particularly for novice raters. Future evaluation of the proposed system in real-world settings (eg, at the microscope) will be needed to further refine criteria and more fully evaluate utility. This improved taxonomy could aid in the understanding of IVD degeneration phenotypes and their association with back pain.
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Affiliation(s)
| | - Chitra L. Dahia
- Orthopaedic Soft Tissue Research ProgramHospital for Special SurgeryNew YorkNew YorkUSA
- Department of Cell and Developmental BiologyWeill Cornell Medicine, Graduate School of Medical SciencesNew YorkNew YorkUSA
| | - Morgan Giers
- School of Chemical, Biological, and Environmental EngineeringOregon State UniversityCorvallisOregonUSA
| | | | - Claudia Cicione
- Laboratory of Regenerative Orthopaedics, Department of Orthopaedic and Trauma SurgeryCampus Bio‐Medico University of RomeRomeItaly
| | - Dino Samartzis
- Department of Orthopaedic SurgeryRush University Medical CenterChicagoIllinoisUSA
- International Spine Research and Innovation InitiativeRush University Medical CenterChicagoIllinoisUSA
| | - Gianluca Vadala
- Laboratory of Regenerative Orthopaedics, Department of Orthopaedic and Trauma SurgeryCampus Bio‐Medico University of RomeRomeItaly
| | - Aaron Fields
- Department of Orthopaedic SurgeryUniversity of California at San FranciscoSan FranciscoCaliforniaUSA
| | - Jeffrey Lotz
- Department of Orthopaedic SurgeryUniversity of California at San FranciscoSan FranciscoCaliforniaUSA
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48
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Menezes-Reis R, Garrido Salmon CE, Bonugli GP, Mazoroski D, Savarese LG, Herrero CFPS, Defino HLA, Nogueira-Barbosa MH. Association between spinal alignment and biochemical composition of lumbar intervertebral discs assessed by quantitative magnetic resonance imaging. Quant Imaging Med Surg 2021; 11:2428-2441. [PMID: 34079713 DOI: 10.21037/qims-20-40] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Background To evaluate potential associations between spinopelvic parameters and the biochemical composition of lumbar intervertebral discs using quantitative magnetic resonance imaging in asymptomatic young adults. Methods Our study group comprised 93 asymptomatic volunteers aged 20-40 years (49 women and 44 men). Lumbar spine T2-weighted images and T2 relaxometry were acquired on a 1.5T MRI scanner. Spinopelvic parameters including sacral slope, pelvic tilt, pelvic incidence, lumbar lordosis, thoracic kyphosis, thoracolumbar alignment, sagittal vertical axis, spinosacral angle, C2 pelvic angle, and T1S1 and L1S1 length were measured on panoramic spine radiographs. Results Lumbar lordosis decrease correlates with discrete dehydration of nucleus pulposus at all lumbar levels. Also low values of sacral slope, pelvic tilt, pelvic incidence, thoracic kyphosis and spinosacral angle were associated with decrease of T2 relaxation times on annulus fibrosus. Conclusions In conclusion, spinopelvic parameters presented a discrete association with lumbar disc composition and water content.
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Affiliation(s)
- Rafael Menezes-Reis
- Ribeirão Preto Medical School - University of São Paulo, Ribeirão Preto, SP, Brazil.,Federal University of Amazonas, Institute of Health and Biotechnology, Coari, AM, Brazil
| | - Carlos E Garrido Salmon
- Ribeirão Preto Philosophy and Sciences School - University of São Paulo, Ribeirão Preto, SP, Brazil
| | - Gustavo P Bonugli
- Ribeirão Preto Medical School - University of São Paulo, Ribeirão Preto, SP, Brazil
| | - Debora Mazoroski
- Ribeirão Preto Medical School - University of São Paulo, Ribeirão Preto, SP, Brazil
| | - Leonor G Savarese
- Ribeirão Preto Medical School - University of São Paulo, Ribeirão Preto, SP, Brazil
| | | | - Helton L A Defino
- Ribeirão Preto Medical School - University of São Paulo, Ribeirão Preto, SP, Brazil
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49
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Yu C, Li D, Wang C, Xia K, Wang J, Zhou X, Ying L, Shu J, Huang X, Xu H, Han B, Chen Q, Li F, Tang J, Liang C, Slater N. Injectable kartogenin and apocynin loaded micelle enhances the alleviation of intervertebral disc degeneration by adipose-derived stem cell. Bioact Mater 2021; 6:3568-3579. [PMID: 33842742 PMCID: PMC8022109 DOI: 10.1016/j.bioactmat.2021.03.018] [Citation(s) in RCA: 28] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/03/2020] [Revised: 02/20/2021] [Accepted: 03/06/2021] [Indexed: 02/06/2023] Open
Abstract
Cell transplantation has been proved the promising therapeutic effects on intervertebral disc degeneration (IVDD). However, the increased levels of reactive oxygen species (ROS) in the degenerated region will impede the efficiency of human adipose-derived stem cells (human ADSCs) transplantation therapy. It inhibits human ADSCs proliferation, and increases human ADSCs apoptosis. Herein, we firstly devised a novel amphiphilic copolymer PEG-PAPO, which could self-assemble into a nanosized micelle and load lipophilic kartogenin (KGN), as a single complex (PAKM). It was an injectable esterase-responsive micelle, and showed controlled release ability of KGN and apocynin (APO). Oxidative stimulation promoted the esterase activity in human ADSCs, which accelerate degradation of esterase-responsive micelle. Compared its monomer, the PAKM micelle possessed better bioactivities, which were attributed to their synergistic effect. It enhanced the viability, autophagic activation (P62, LC3 II), ECM-related transcription factor (SOX9), and ECM (Collagen II, Aggrecan) maintenance in human ADSCs. Furthermore, it is demonstrated that the injection of PAKM with human ADSCs yielded higher disc height and water content in rats. Therefore, PAKM micelles perform promoting cell survival and differentiation effects, and may be a potential therapeutic agent for IVDD.
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Affiliation(s)
- Chao Yu
- Department of Orthopedics Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou City, Zhejiang Province, PR China.,Orthopedics Research Institute of Zhejiang University, Hangzhou City, Zhejiang Province, PR China.,Key Laboratory of Motor System Disease Research and Precision Therapy of Zhejiang Province, Hangzhou City, Zhejiang Province, PR China
| | - Dongdong Li
- Key Laboratory of Biomass Chemical Engineering of Ministry of Education, Center for Bionanoengineering, and College of Chemical and Biological Engineering, Zhejiang University, Hangzhou, Zhejiang, 310027, China
| | - Chenggui Wang
- Department of Orthopedics Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou City, Zhejiang Province, PR China.,Orthopedics Research Institute of Zhejiang University, Hangzhou City, Zhejiang Province, PR China.,Key Laboratory of Motor System Disease Research and Precision Therapy of Zhejiang Province, Hangzhou City, Zhejiang Province, PR China
| | - Kaishun Xia
- Department of Orthopedics Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou City, Zhejiang Province, PR China.,Orthopedics Research Institute of Zhejiang University, Hangzhou City, Zhejiang Province, PR China.,Key Laboratory of Motor System Disease Research and Precision Therapy of Zhejiang Province, Hangzhou City, Zhejiang Province, PR China
| | - Jingkai Wang
- Department of Orthopedics Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou City, Zhejiang Province, PR China.,Orthopedics Research Institute of Zhejiang University, Hangzhou City, Zhejiang Province, PR China.,Key Laboratory of Motor System Disease Research and Precision Therapy of Zhejiang Province, Hangzhou City, Zhejiang Province, PR China
| | - Xiaopeng Zhou
- Department of Orthopedics Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou City, Zhejiang Province, PR China.,Orthopedics Research Institute of Zhejiang University, Hangzhou City, Zhejiang Province, PR China.,Key Laboratory of Motor System Disease Research and Precision Therapy of Zhejiang Province, Hangzhou City, Zhejiang Province, PR China
| | - Liwei Ying
- Department of Orthopedics Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou City, Zhejiang Province, PR China.,Orthopedics Research Institute of Zhejiang University, Hangzhou City, Zhejiang Province, PR China.,Key Laboratory of Motor System Disease Research and Precision Therapy of Zhejiang Province, Hangzhou City, Zhejiang Province, PR China
| | - Jiawei Shu
- Department of Orthopedics Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou City, Zhejiang Province, PR China.,Orthopedics Research Institute of Zhejiang University, Hangzhou City, Zhejiang Province, PR China.,Key Laboratory of Motor System Disease Research and Precision Therapy of Zhejiang Province, Hangzhou City, Zhejiang Province, PR China
| | - Xianpeng Huang
- Department of Orthopedics Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou City, Zhejiang Province, PR China.,Orthopedics Research Institute of Zhejiang University, Hangzhou City, Zhejiang Province, PR China.,Key Laboratory of Motor System Disease Research and Precision Therapy of Zhejiang Province, Hangzhou City, Zhejiang Province, PR China
| | - Haibin Xu
- Department of Orthopedics Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou City, Zhejiang Province, PR China.,Orthopedics Research Institute of Zhejiang University, Hangzhou City, Zhejiang Province, PR China.,Key Laboratory of Motor System Disease Research and Precision Therapy of Zhejiang Province, Hangzhou City, Zhejiang Province, PR China
| | - Bin Han
- Department of Orthopedics Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou City, Zhejiang Province, PR China.,Orthopedics Research Institute of Zhejiang University, Hangzhou City, Zhejiang Province, PR China.,Key Laboratory of Motor System Disease Research and Precision Therapy of Zhejiang Province, Hangzhou City, Zhejiang Province, PR China
| | - Qixin Chen
- Department of Orthopedics Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou City, Zhejiang Province, PR China.,Orthopedics Research Institute of Zhejiang University, Hangzhou City, Zhejiang Province, PR China.,Key Laboratory of Motor System Disease Research and Precision Therapy of Zhejiang Province, Hangzhou City, Zhejiang Province, PR China
| | - Fangcai Li
- Department of Orthopedics Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou City, Zhejiang Province, PR China.,Orthopedics Research Institute of Zhejiang University, Hangzhou City, Zhejiang Province, PR China.,Key Laboratory of Motor System Disease Research and Precision Therapy of Zhejiang Province, Hangzhou City, Zhejiang Province, PR China
| | - Jianbin Tang
- Key Laboratory of Biomass Chemical Engineering of Ministry of Education, Center for Bionanoengineering, and College of Chemical and Biological Engineering, Zhejiang University, Hangzhou, Zhejiang, 310027, China
| | - Chengzhen Liang
- Department of Orthopedics Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou City, Zhejiang Province, PR China.,Orthopedics Research Institute of Zhejiang University, Hangzhou City, Zhejiang Province, PR China.,Key Laboratory of Motor System Disease Research and Precision Therapy of Zhejiang Province, Hangzhou City, Zhejiang Province, PR China
| | - Nigel Slater
- Department of Chemical Engineering and Biotechnology, University of Cambridge, Cambridge, United Kingdom
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50
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Liu L, He J, Liu C, Yang M, Fu J, Yi J, Ai X, Liu M, Zhuang Y, Zhang Y, Huang B, Li C, Zhou Y, Feng C. Cartilage intermediate layer protein affects the progression of intervertebral disc degeneration by regulating the extracellular microenvironment (Review). Int J Mol Med 2021; 47:475-484. [PMID: 33416131 PMCID: PMC7797476 DOI: 10.3892/ijmm.2020.4832] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/18/2020] [Accepted: 11/27/2020] [Indexed: 12/25/2022] Open
Abstract
Intervertebral disc degeneration (IDD), which is caused by multiple factors, affects the health of individuals and contributes to low back pain. The pathology of IDD is complicated, and changes in the extracellular microenvironment play an important role in promoting the process of degeneration. Cartilage intermediate layer protein (CILP) is a matrix protein that resides in the middle of human articular cartilage and is involved in numerous diseases that affect cartilage. However, there is no detailed review of the relationship between CILP and degenerative disc disease. Growing evidence has revealed the presence of CILP in the extracellular microenvironment of intervertebral discs (IVDs) and has suggested that there is a gradual increase in CILP in degenerative discs. Specifically, CILP plays an important role in regulating the metabolism of the extracellular matrix (ECM), an important component of the extracellular microenvironment. CILP can combine with transforming growth factor‑β or insulin‑like growth factor‑1 to regulate the ECM synthesis of IVDs and influence the balance of ECM metabolism, which leads to changes in the extracellular microenvironment to promote the process of IDD. It may be possible to show the correlation of CILP with IDD and to target CILP to interfere with IDD. For this purpose, in the present study, the current knowledge on CILP was summarized and a detailed description of CILP in discs was provided.
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Affiliation(s)
- Libangxi Liu
- Department of Orthopedics, Xinqiao Hospital, Army Medical University
| | - Jinyue He
- Department of Orthopedics, Xi'nan Hospital, Army Medical University, Chongqing 400037
| | - Chang Liu
- Department of Orthopedics, Xinqiao Hospital, Army Medical University
| | - Minghui Yang
- Department of Orthopedics, Xinqiao Hospital, Army Medical University
| | - Jiawei Fu
- Department of Orthopedics, Xinqiao Hospital, Army Medical University
| | - Jiarong Yi
- Department of Orthopedics, Xinqiao Hospital, Army Medical University
| | - Xuezheng Ai
- Department of Orthopedics, Xinqiao Hospital, Army Medical University
| | - Miao Liu
- Department of Orthopedics, Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou 550004, P.R. China
| | - Yong Zhuang
- Department of Orthopedics, Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou 550004, P.R. China
| | - Yaqing Zhang
- Department of Orthopedics, Xinqiao Hospital, Army Medical University
| | - Bo Huang
- Department of Orthopedics, Xinqiao Hospital, Army Medical University
| | - Changqing Li
- Department of Orthopedics, Xinqiao Hospital, Army Medical University
| | - Yue Zhou
- Department of Orthopedics, Xinqiao Hospital, Army Medical University
| | - Chencheng Feng
- Department of Orthopedics, Xinqiao Hospital, Army Medical University
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