|
1
|
Zheng Z, Yang M, Zhang Z, Zhu Y, Huang H, Wang J. Inverse L-shaped association of triglyceride glucose index with all-cause and cerebral cardiovascular-related mortality in osteoarthritis patients: a cohort of 4145 patients. Clin Rheumatol 2025; 44:1831-1841. [PMID: 40067575 DOI: 10.1007/s10067-025-07376-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/28/2024] [Revised: 01/22/2025] [Accepted: 02/16/2025] [Indexed: 04/13/2025]
Abstract
BACKGROUND Currently, osteoarthritis (OA) is recognized as a systemic disease, wherein metabolic disturbances play a part in joint degeneration and elevated risk of mortality. This study investigates the prognostic value of the triglyceride-glucose (TyG) index in determining all-cause and cerebral cardiovascular mortality among OA patients, accentuating the necessity for customized interventions. METHODS A cohort of osteoarthritis patients from the 1999-2018 NHANES was linked to the 2019 National Death Index (NDI) for mortality confirmation. TyG index correlation with all-cause and cerebral cardiovascular mortality was assessed using Cox regression and Kaplan-Meier curves. Non-linear associations were examined with restricted cubic splines, and a two-piecewise Cox model was built around the inflection point. RESULTS A total of 4145 OA patients were followed for a median of 89 months, during which 1109 all-cause deaths and 427 cerebral cardiovascular-related deaths were observed. Restricted cubic splines showed an inverse L-shaped relationship between the TyG index and both types of mortality. The critical point was identified as 9.48, with a 1-unit increase associated with a 71% and 91% rise in adjusted all-cause and cerebral cardiovascular mortality, respectively (HR 1.71; 95% CI 1.30, 2.26 and HR 1.91; 95% CI 1.28, 2.86). Subgroup analyses revealed significant associations between the TyG index and elevated mortality risks among non-white OA patients and those with concurrent diabetes. CONCLUSION In OA patients, the TyG index and mortality (both all-cause and cerebral cardiovascular) share an inverse L-shaped relationship, with identified thresholds at 9.48. This threshold offers valuable insight for risk assessment, thus promoting a shift towards personalized healthcare strategies founded on metabolic status for enhanced outcomes within OA populations. Key points • The TyG index predicts all-cause and cerebral cardiovascular mortality in OA patients. • An inverse L-shaped relationship between the TyG index and mortality was found, with a critical threshold of 9.48. • Non-white OA patients and those with diabetes show significant associations with elevated mortality risks, highlighting the importance of personalized care.
Collapse
Affiliation(s)
- Zitian Zheng
- Department of Sports Medicine, Peking University Third Hospital, Institute of Sports Medicine of Peking University, Beijing, 100191, P. R. China
- Beijing Key Laboratory of Sports Injuries, Beijing, 100191, P. R. China
- Engineering Research Center of Sports Trauma Treatment Technology and Devices, Ministry of Education, Beijing, 100191, P. R. China
| | - Meng Yang
- Department of Sports Medicine, Peking University Third Hospital, Institute of Sports Medicine of Peking University, Beijing, 100191, P. R. China
- Beijing Key Laboratory of Sports Injuries, Beijing, 100191, P. R. China
- Engineering Research Center of Sports Trauma Treatment Technology and Devices, Ministry of Education, Beijing, 100191, P. R. China
| | - Zhiyu Zhang
- Department of Sports Medicine, Peking University Third Hospital, Institute of Sports Medicine of Peking University, Beijing, 100191, P. R. China
- Beijing Key Laboratory of Sports Injuries, Beijing, 100191, P. R. China
- Engineering Research Center of Sports Trauma Treatment Technology and Devices, Ministry of Education, Beijing, 100191, P. R. China
| | - Yucheng Zhu
- Department of Sports Medicine, Peking University Third Hospital, Institute of Sports Medicine of Peking University, Beijing, 100191, P. R. China
- Beijing Key Laboratory of Sports Injuries, Beijing, 100191, P. R. China
- Engineering Research Center of Sports Trauma Treatment Technology and Devices, Ministry of Education, Beijing, 100191, P. R. China
| | - Hongjie Huang
- Department of Sports Medicine, Peking University Third Hospital, Institute of Sports Medicine of Peking University, Beijing, 100191, P. R. China.
- Beijing Key Laboratory of Sports Injuries, Beijing, 100191, P. R. China.
- Engineering Research Center of Sports Trauma Treatment Technology and Devices, Ministry of Education, Beijing, 100191, P. R. China.
| | - Jianquan Wang
- Department of Sports Medicine, Peking University Third Hospital, Institute of Sports Medicine of Peking University, Beijing, 100191, P. R. China.
- Beijing Key Laboratory of Sports Injuries, Beijing, 100191, P. R. China.
- Engineering Research Center of Sports Trauma Treatment Technology and Devices, Ministry of Education, Beijing, 100191, P. R. China.
| |
Collapse
|
|
2
|
Alrawaili SM, Alkhathami KM, Elsehrawy MG, Alghamdi MS, Alhwoaimel NA, Alenazi AM. The Coexistence of Hypertension and Arthritis Was Not Associated with Pain Severity in Community-Dwelling Older Adults in the United States. Healthcare (Basel) 2025; 13:570. [PMID: 40077132 PMCID: PMC11899035 DOI: 10.3390/healthcare13050570] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2025] [Revised: 03/01/2025] [Accepted: 03/04/2025] [Indexed: 03/14/2025] Open
Abstract
Background and Aim: Current evidence suggests that both arthritis and hypertension (HTN) can contribute to an increase in pain severity, potentially owing to shared pathophysiological pathways. However, the extent to which these conditions jointly affect pain severity has not been well studied. The aim of this study was to explore the association between the coexistence of HTN and arthritis and their impact on pain severity among community-dwelling older adults. Methods: A cross-sectional design was used. Data from the Wave 2 (2010-2011) of the National Social Life, Health, and Aging Project (NSHAP) were used. Participants were community-dwelling older adults and categorized based on self-reported diagnoses into four groups: combined HTN and arthritis, HTN only, arthritis only, and neither. Pain severity was measured using the Verbal Descriptor Scale (VDS). Multiple generalized linear regression analyses were conducted with adjustments for age, sex, race, body mass index, educational level, and the use of pain and hypertension medications. Results: Data for 1754 participants were analyzed. The prevalence of combined HTN and arthritis was 28.4%. The prevalence of HTN only and arthritis only was 35.2% and 14.2%, respectively. Participants with both HTN and arthritis had higher pain severity compared to those with neither or only one of these conditions. After covariate adjustment, the combined HTN and arthritis group showed a significant association with higher pain severity (B = 0.39, p < 0.001). Similarly, the arthritis-only group also demonstrated a significant association with increased pain severity (B = 0.26, p = 0.002). However, the HTN alone showed no significant associations with pain severity (B = 0.014, p = 0.83). Compared to the arthritis-only group, combined HTN and arthritis showed a significant association with pain severity (B = 0.16, p = 0.049) in an unadjusted model only, and this association disappeared after adjusting for covariates (B = 0.15, p = 0.08). Conclusions: This study found no significant association between coexisting HTN and arthritis compared to arthritis alone after adjusting for covariates among community-dwelling older adults. The influence of covariates highlights the multifaceted nature of pain determinants, which emphasize the need for a multidisciplinary approach to pain management to enhance their functional capacity and overall quality of life.
Collapse
Affiliation(s)
- Saud M. Alrawaili
- Department of Health and Rehabilitation Sciences, Prince Sattam Bin Abdulaziz University, Al-Kharj 11942, Saudi Arabia; (S.M.A.); (N.A.A.)
| | - Khalid M. Alkhathami
- Department of Health Rehabilitation, Shaqra University, Shaqra 11961, Saudi Arabia;
| | - Mohammed G. Elsehrawy
- Department of Nursing, Prince Sattam Bin Abdulaziz University, Al-Kharj 11942, Saudi Arabia;
| | - Mohammed S. Alghamdi
- Department of Medical Rehabilitation Sciences, Faculty of Applied Medical Sciences, Umm Al-Qura University, Makkah 24382, Saudi Arabia;
| | - Norah A. Alhwoaimel
- Department of Health and Rehabilitation Sciences, Prince Sattam Bin Abdulaziz University, Al-Kharj 11942, Saudi Arabia; (S.M.A.); (N.A.A.)
| | - Aqeel M. Alenazi
- Department of Health and Rehabilitation Sciences, Prince Sattam Bin Abdulaziz University, Al-Kharj 11942, Saudi Arabia; (S.M.A.); (N.A.A.)
| |
Collapse
|
|
3
|
Ma Y, Pang Y, Cao R, Zheng Z, Zheng K, Tian Y, Peng X, Liu D, Du D, Du L, Zhong Z, Yao L, Zhang C, Gao J. Targeting Parkin-regulated metabolomic change in cartilage in the treatment of osteoarthritis. iScience 2024; 27:110597. [PMID: 39220257 PMCID: PMC11363567 DOI: 10.1016/j.isci.2024.110597] [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] [Received: 02/16/2024] [Revised: 04/28/2024] [Accepted: 07/24/2024] [Indexed: 09/04/2024] Open
Abstract
Articular cartilage degeneration may lead to osteoarthritis (OA) during the aging process, but its underlying mechanism remains unknown. Here, we found that chondrocytes exhibited an energy metabolism shift from glycolysis to oxidative phosphorylation (OXPHOS) during aging. Parkin regulates various cellular metabolic processes. Reprogrammed cartilage metabolism by Parkin ablation decreased OXPHOS and increased glycolysis, with ameliorated aging-related OA. Metabolomics analysis indicated that lauroyl-L-carnitine (LLC) was decreased in aged cartilage, but increased in Parkin-deficient cartilage. In vitro, LLC improved the cartilage matrix synthesis of aged chondrocytes. In vivo, intra-articular injection of LLC in mice with anterior cruciate ligament transaction (ACLT) ameliorated OA progression. These results suggest that metabolic changes are regulated by Parkin-impaired cartilage during aging, and targeting this metabolomic changes by supplementation with LLC is a promising treatment strategy for ameliorating OA.
Collapse
Affiliation(s)
- Yiyang Ma
- Department of Orthopaedics, Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200233, China
- Institute of Microsurgery on Extremities, and Department of Orthopedic Surgery, Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200233, China
| | - Yidan Pang
- Department of Orthopaedics, Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200233, China
- Institute of Microsurgery on Extremities, and Department of Orthopedic Surgery, Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200233, China
| | - Ruomu Cao
- Department of Bone and Joint Surgery, the Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shanxi 710004, China
| | - Zhikai Zheng
- Department of Orthopaedics, Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200233, China
- Institute of Microsurgery on Extremities, and Department of Orthopedic Surgery, Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200233, China
| | - Kaiwen Zheng
- Department of Orthopaedics, Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200233, China
- Institute of Microsurgery on Extremities, and Department of Orthopedic Surgery, Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200233, China
| | - Yucheng Tian
- Department of Orthopaedics, Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200233, China
- Institute of Microsurgery on Extremities, and Department of Orthopedic Surgery, Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200233, China
| | - Xiaoyuan Peng
- Department of Orthopaedics, Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200233, China
| | - Delin Liu
- Department of Orthopaedics, Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200233, China
- Institute of Microsurgery on Extremities, and Department of Orthopedic Surgery, Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200233, China
| | - Dajiang Du
- Department of Orthopaedics, Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200233, China
| | - Lin Du
- Orthopedics Department, The First Affiliated Hospital of Shantou University Medical College, Shantou 515041, China
- Sports Medicine Institute, Shantou University Medical College, Shantou 515041, China
| | - Zhigang Zhong
- Orthopedics Department, The First Affiliated Hospital of Shantou University Medical College, Shantou 515041, China
- Sports Medicine Institute, Shantou University Medical College, Shantou 515041, China
| | - Lufeng Yao
- Department of Orthopaedic Surgery, Ningbo No.6 Hospital, No.1059 East Zhongshan Road, Yinzhou District, Ningbo, Zhejiang 315040, China
| | - Changqing Zhang
- Department of Orthopaedics, Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200233, China
- Institute of Microsurgery on Extremities, and Department of Orthopedic Surgery, Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200233, China
| | - Junjie Gao
- Department of Orthopaedics, Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200233, China
- Institute of Microsurgery on Extremities, and Department of Orthopedic Surgery, Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200233, China
| |
Collapse
|
|
4
|
Diao Z, Guo D, Zhang J, Zhang R, Li C, Chen H, Ma Y. Causal relationship between modifiable risk factors and knee osteoarthritis: a Mendelian randomization study. Front Med (Lausanne) 2024; 11:1405188. [PMID: 39286647 PMCID: PMC11402680 DOI: 10.3389/fmed.2024.1405188] [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] [Received: 03/22/2024] [Accepted: 05/28/2024] [Indexed: 09/19/2024] Open
Abstract
Background While several risk factors for knee osteoarthritis (KOA) have been recognized, the pathogenesis of KOA and the causal relationship between modifiable risk factors and KOA in genetic epidemiology remain unclear. This study aimed to determine the causal relationship between KOA and its risk factors. Methods Data were obtained from published Genome-Wide Association study (GWAS) databases. A two-sample Mendelian randomization (MR) analysis was performed with genetic variants associated with risk factors as instrumental variables and KOA as outcome. First, inverse variance weighting was used as the main MR analysis method, and then a series of sensitivity analyses were conducted to comprehensively evaluate the causal relationship between them. Results Univariate forward MR analysis revealed that genetically predicted hypothyroidism, hyperthyroidism/thyrotoxicosis, educational level, income level, metabolic syndrome (MS), essential hypertension, height, hot drink temperature, diet (abstaining from sugar-sweetened or wheat products), and psychological and psychiatric disorders (stress, depression, and anxiety) were causally associated with KOA. Reverse MR exhibits a causal association between KOA and educational attainment. Multivariate MR analysis adjusted for the inclusion of potential mediators, such as body mass index (BMI), smoking, alcohol consumption, and sex, exhibited some variation in causal effects. However, hyperthyroidism/thyrotoxicosis had a significant causal effect on KOA, and there was good evidence that height, hypothyroidism, educational level, psychological and psychiatric disorders (stress, depression, and anxiety), and abstaining from wheat products had an independent causal relationship. The mediating effect of BMI as a mediator was also identified. Conclusion This study used MR to validate the causal relationship between KOA and its risk factors, providing new insights for preventing and treating KOA in clinical practice and for developing public health policies.
Collapse
Affiliation(s)
- Zhihao Diao
- School of Acupuncture and Tuina, Shandong University of Traditional Chinese Medicine, Jinan, China
| | - Danyang Guo
- The First Clinical Medical College, Shandong University of Traditional Chinese Medicine, Jinan, China
| | - Jingzhi Zhang
- School of Acupuncture and Tuina, Shandong University of Traditional Chinese Medicine, Jinan, China
| | - Ruiyu Zhang
- School of Acupuncture and Tuina, Shandong University of Traditional Chinese Medicine, Jinan, China
| | - Chunjing Li
- School of Acupuncture and Tuina, Shandong University of Traditional Chinese Medicine, Jinan, China
| | - Hao Chen
- Complutense University of Madrid, Madrid, Spain
| | - Yuxia Ma
- School of Acupuncture and Tuina, Shandong University of Traditional Chinese Medicine, Jinan, China
| |
Collapse
|
|
5
|
Giannopapas V, Smyrni V, Kitsos DK, Stasi S, Chasiotis AK, Moschovos C, Papagiannopoulou G, Stavrogianni K, Kosmidou M, Bakalidou D, Tzartos JS, Tsivgoulis G, Giannopoulos S. Osteoarthritis in People with Multiple Sclerosis: A Systematic Review and Meta-Analysis. J Clin Med 2024; 13:5015. [PMID: 39274226 PMCID: PMC11396250 DOI: 10.3390/jcm13175015] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2024] [Revised: 08/20/2024] [Accepted: 08/22/2024] [Indexed: 09/16/2024] Open
Abstract
Background: Arthritis, particularly osteoarthritis (OA), is a common synovial condition observed in individuals with multiple sclerosis (MS). Despite its high prevalence and significant impact on the quality of life of MS individuals, there is a gap in the current literature regarding the prevalence of OA in this population and its relation to MS pathology. This systematic review and meta-analysis aimed to estimate the prevalence of OA in the MS population and explore potential associations with demographic and MS-specific characteristics. Methods: Adhering to PRISMA guidelines, a systematic search of the MEDLINE PubMed, Scopus and Google Scholar databases was conducted. Results: Fifteen studies were included in the systematic review and meta-analysis. The aggregated prevalence of OA in the MS population was 27% (95% CI: 15-40%), with substantial heterogeneity (I2 = 99.9%). Sensitivity analysis, excluding one study, showed a prevalence of 21% (95% CI: 16-28%). The risk ratio of OA in MS versus controls was 1.07 (95% CI: 0.84-1.37), indicating no significant difference. Meta-regression revealed no associations between OA prevalence and age or disease duration in MS patients. Conclusions: This study reports a 21-27% prevalence of OA in people with MS. Understanding the implications of OA in pain and mobility domains, as well as the challenges in distinguishing OA symptoms from MS manifestations, underscores the need for further research to elucidate the pathophysiological mechanisms and interactions between these conditions. Additional studies are warranted to enhance clinical management and improve outcomes for individuals with MS and co-existing OA.
Collapse
Affiliation(s)
- Vasileios Giannopapas
- Second Department of Neurology, National and Kapodistrian University of Athens, 15772 Athens, Greece
- Department of Physical Therapy, University of West Attica, 12243 Egaleo, Greece
| | - Vassiliki Smyrni
- Second Department of Neurology, National and Kapodistrian University of Athens, 15772 Athens, Greece
| | - Dimitrios K Kitsos
- Second Department of Neurology, National and Kapodistrian University of Athens, 15772 Athens, Greece
| | - Sophia Stasi
- Department of Physical Therapy, University of Peloponnese, 23100 Sparti, Greece
| | - Athanasios K Chasiotis
- Second Department of Neurology, National and Kapodistrian University of Athens, 15772 Athens, Greece
- Department of Physical Therapy, University of West Attica, 12243 Egaleo, Greece
| | - Christos Moschovos
- Second Department of Neurology, National and Kapodistrian University of Athens, 15772 Athens, Greece
| | - Georgia Papagiannopoulou
- Second Department of Neurology, National and Kapodistrian University of Athens, 15772 Athens, Greece
| | - Konstantina Stavrogianni
- Second Department of Neurology, National and Kapodistrian University of Athens, 15772 Athens, Greece
- Department of Physiology, Faculty of Medicine, University of Ioannina, 45110 Ioannina, Greece
| | - Maria Kosmidou
- Department of Internal Medicine, Faculty of Medicine, University of Ioannina, 45110 Ioannina, Greece
| | - Daphne Bakalidou
- Second Department of Neurology, National and Kapodistrian University of Athens, 15772 Athens, Greece
| | - John S Tzartos
- Second Department of Neurology, National and Kapodistrian University of Athens, 15772 Athens, Greece
| | - Georgios Tsivgoulis
- Second Department of Neurology, National and Kapodistrian University of Athens, 15772 Athens, Greece
| | - Sotirios Giannopoulos
- Second Department of Neurology, National and Kapodistrian University of Athens, 15772 Athens, Greece
| |
Collapse
|
|
6
|
Singh A, Kotzur T, Vivancos-Koopman I, Emukah C, Brady C, Martin C. A component-based analysis of metabolic syndrome's impact on 30-day outcomes after hip fracture: reduced mortality in obese patients. OTA Int 2024; 7:e301. [PMID: 38292467 PMCID: PMC10827291 DOI: 10.1097/oi9.0000000000000301] [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] [Indexed: 02/01/2024]
Abstract
Introduction Hip fractures are a common injury associated with significant morbidity and mortality. In the United States, there has been a rapid increase in the prevalence of metabolic syndrome (MetS), a condition comprised several common comorbidities, including obesity, diabetes mellitus, and hypertension, that may worsen perioperative outcomes. This article assesses the impact of MetS and its components on outcomes after hip fracture surgery. Methods Patients who underwent nonelective operative treatment for traumatic hip fractures were identified in the 2015-2020 American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) database. Baseline characteristics between groups were compared, and significant differences were included as covariates. Multivariate regression was performed to assess the impact of characteristics of interest on postoperative outcomes. Patients with MetS, or a single one of its constitutive components-hypertension, diabetes, and obesity-were compared with metabolically healthy cohorts. Results In total 95,338 patients were included. Patients with MetS had increased complications (OR 1.509; P < 0.001), but reduced mortality (OR 0.71; P < 0.001). Obesity alone was also associated with increased complications (OR 1.14; P < 0.001) and reduced mortality (OR 0.736; P < 0.001). Both hypertension and diabetes alone increased complications (P < 0.001) but had no impact on mortality. Patients with MetS did, however, have greater odds of adverse discharge (OR 1.516; P < 0.001), extended hospital stays (OR 1.18; P < 0.001), and reoperation (OR 1.297; P = 0.003), but no significant difference in readmission rate. Conclusion Patients with MetS had increased complications but decreased mortality. Our component-based analysis showed had obesity had a similar effect: increased complications but lower mortality. These results may help surgeons preoperatively counsel patients with hip fracture about their postoperative risks.
Collapse
Affiliation(s)
- Aaron Singh
- Department of Orthopaedics, UT Health San Antonio, San Antonio, TX
| | - Travis Kotzur
- Department of Orthopaedics, UT Health San Antonio, San Antonio, TX
| | | | - Chimobi Emukah
- Department of Orthopaedics, UT Health San Antonio, San Antonio, TX
| | - Christina Brady
- Department of Orthopaedics, UT Health San Antonio, San Antonio, TX
| | - Case Martin
- Department of Orthopaedics, UT Health San Antonio, San Antonio, TX
| |
Collapse
|
|
7
|
Alemany M. The Metabolic Syndrome, a Human Disease. Int J Mol Sci 2024; 25:2251. [PMID: 38396928 PMCID: PMC10888680 DOI: 10.3390/ijms25042251] [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: 12/01/2023] [Revised: 01/29/2024] [Accepted: 01/31/2024] [Indexed: 02/25/2024] Open
Abstract
This review focuses on the question of metabolic syndrome (MS) being a complex, but essentially monophyletic, galaxy of associated diseases/disorders, or just a syndrome of related but rather independent pathologies. The human nature of MS (its exceptionality in Nature and its close interdependence with human action and evolution) is presented and discussed. The text also describes the close interdependence of its components, with special emphasis on the description of their interrelations (including their syndromic development and recruitment), as well as their consequences upon energy handling and partition. The main theories on MS's origin and development are presented in relation to hepatic steatosis, type 2 diabetes, and obesity, but encompass most of the MS components described so far. The differential effects of sex and its biological consequences are considered under the light of human social needs and evolution, which are also directly related to MS epidemiology, severity, and relations with senescence. The triggering and maintenance factors of MS are discussed, with especial emphasis on inflammation, a complex process affecting different levels of organization and which is a critical element for MS development. Inflammation is also related to the operation of connective tissue (including the adipose organ) and the widely studied and acknowledged influence of diet. The role of diet composition, including the transcendence of the anaplerotic maintenance of the Krebs cycle from dietary amino acid supply (and its timing), is developed in the context of testosterone and β-estradiol control of the insulin-glycaemia hepatic core system of carbohydrate-triacylglycerol energy handling. The high probability of MS acting as a unique complex biological control system (essentially monophyletic) is presented, together with additional perspectives/considerations on the treatment of this 'very' human disease.
Collapse
Affiliation(s)
- Marià Alemany
- Faculty of Biology, Universitat de Barcelona, 08028 Barcelona, Catalonia, Spain
| |
Collapse
|
|
8
|
Lu Z, Mao T, Chen K, Chai L, Dai Y, Liu K. Ginsenoside Rc: A potential intervention agent for metabolic syndrome. J Pharm Anal 2023; 13:1375-1387. [PMID: 38223453 PMCID: PMC10785250 DOI: 10.1016/j.jpha.2023.08.013] [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] [Received: 05/12/2023] [Revised: 07/26/2023] [Accepted: 08/16/2023] [Indexed: 01/16/2024] Open
Abstract
Ginsenoside Rc, a dammarane-type tetracyclic triterpenoid saponin primarily derived from Panax ginseng, has garnered significant attention due to its diverse pharmacological properties. This review outlined the sources, putative biosynthetic pathways, extraction, and quantification techniques, as well as the pharmacokinetic properties of ginsenoside Rc. Furthermore, this study explored the pharmacological effects of ginsenoside Rc against metabolic syndrome (MetS) across various phenotypes including obesity, diabetes, atherosclerosis, non-alcoholic fatty liver disease, and osteoarthritis. It also highlighted the impact of ginsenoside Rc on multiple associated signaling molecules. In conclusion, the anti-MetS effect of ginsenoside Rc is characterized by its influence on multiple organs, multiple targets, and multiple ways. Although clinical investigations regarding the effects of ginsenoside Rc on MetS are limited, its proven safety and tolerability suggest its potential as an effective treatment option.
Collapse
Affiliation(s)
- Zhengjie Lu
- Department of Pharmacy, Zhongnan Hospital of Wuhan University, Wuhan, 430072, China
- Department of Orthopedic Surgery, Zhongnan Hospital of Wuhan University, Wuhan, 430072, China
- Department of Pharmacology, Wuhan University School of Basic Medical Sciences, Wuhan, 430071, China
| | - Tongyun Mao
- Department of Pharmacology, Wuhan University School of Basic Medical Sciences, Wuhan, 430071, China
| | - Kaiqi Chen
- Department of Pharmacology, Wuhan University School of Basic Medical Sciences, Wuhan, 430071, China
| | - Longxin Chai
- School of Life Sciences, Hubei University, Wuhan, 430062, China
| | - Yongguo Dai
- Department of Pharmacology, Wuhan University School of Basic Medical Sciences, Wuhan, 430071, China
| | - Kexin Liu
- Department of Pharmacy, Zhongnan Hospital of Wuhan University, Wuhan, 430072, China
- Department of Pharmacology, Wuhan University School of Basic Medical Sciences, Wuhan, 430071, China
| |
Collapse
|
|
9
|
Xing X, Wang Y, Pan F, Cai G. Osteoarthritis and risk of type 2 diabetes: A two-sample Mendelian randomization analysis. J Diabetes 2023; 15:987-993. [PMID: 37525375 PMCID: PMC10667649 DOI: 10.1111/1753-0407.13451] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/28/2023] [Revised: 05/29/2023] [Accepted: 07/14/2023] [Indexed: 08/02/2023] Open
Abstract
BACKGROUND Physical inactivity is an independent risk factor for type 2 diabetes (T2D). Osteoarthritis (OA) is a common joint disease that limits patients' physical activity, which may increase risk of other chronic diseases including T2D. However, studies evaluating the effect of OA on T2D are scarce. This study aimed to investigate the causal effect of knee and hip OA on risk of T2D from a genetic perspective. METHODS We performed two-sample Mendelian randomization (MR) analyses to obtain nonconfounding estimates of the effect of OA on T2D risk. Single nucleotide polymorphisms (SNPs) from genome-wide association studies were selected as genetic instruments for radiographic knee and hip OA (ie, Kellgren-Lawrence grade ≥2). The associations of these SNPs with T2D were evaluated in participants from the UK Biobank. Sensitivity analyses were conducted to test the robustness of the MR results. RESULTS Genetic predisposition of knee but not hip OA was significantly associated with an increased risk of T2D (knee OA: odds ratio [OR] 1.18, 95% confidence interval (CI) 1.09-1.27, p <.001; hip OA: OR 1.04, 95% CI 0.94-1.16, p = .425). Sensitivity analyses showed that the main findings are robust. CONCLUSION The current study provides genetic evidence supporting that knee OA is a potential risk factor for T2D.
Collapse
Affiliation(s)
- Xing Xing
- Department of Epidemiology and Biostatistics, School of Public HealthAnhui Medical UniversityHefeiChina
| | - Yining Wang
- Department of Epidemiology and Biostatistics, School of Public HealthAnhui Medical UniversityHefeiChina
| | - Faming Pan
- Department of Epidemiology and Biostatistics, School of Public HealthAnhui Medical UniversityHefeiChina
- The Inflammation and Immune Mediated Diseases Laboratory of Anhui ProvinceAnhui Medical UniversityHefeiChina
| | - Guoqi Cai
- Department of Epidemiology and Biostatistics, School of Public HealthAnhui Medical UniversityHefeiChina
- Menzies Institute for Medical Research, University of TasmaniaHobartAustralia
| |
Collapse
|
|
10
|
Ely EV, Kapinski AT, Paradi SG, Tang R, Guilak F, Collins KH. Designer Fat Cells: Adipogenic Differentiation of CRISPR-Cas9 Genome-Engineered Induced Pluripotent Stem Cells. BIORXIV : THE PREPRINT SERVER FOR BIOLOGY 2023:2023.10.26.564206. [PMID: 37961399 PMCID: PMC10634849 DOI: 10.1101/2023.10.26.564206] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/15/2023]
Abstract
Adipose tissue is an active endocrine organ that can signal bidirectionally to many tissues and organ systems in the body. With obesity, adipose tissue is a source of low-level inflammation that contributes to various co-morbidities and damage to downstream effector tissues. The ability to synthesize genetically engineered adipose tissue could have critical applications in studying adipokine signaling and the use of adipose tissue for novel therapeutic strategies. This study aimed to develop a method for non-viral adipogenic differentiation of genome-edited murine induced pluripotent stem cells (iPSCs) and to test the ability of such cells to engraft in mice in vivo . Designer adipocytes were created from iPSCs, which can be readily genetically engineered using CRISPR-Cas9 to knock out or insert individual genes of interest. As a model system for adipocyte-based drug delivery, an existing iPSC cell line that transcribes interleukin 1 receptor antagonist under the endogenous macrophage chemoattractant protein-1 promoter was tested for adipogenic capabilities under these same differentiation conditions. To understand the role of various adipocyte subtypes and their impact on health and disease, an efficient method was devised for inducing browning and whitening of IPSC-derived adipocytes in culture. Finally, to study the downstream effects of designer adipocytes in vivo , we transplanted the designer adipocytes into fat-free lipodystrophic mice as a model system for studying adipose signaling in different models of disease or repair. This novel translational tissue engineering and regenerative medicine platform provides an innovative approach to studying the role of adipose interorgan communication in various conditions.
Collapse
|
|
11
|
Alenazi AM, Alkhathami KM. Hypertension Is Associated with Joint Pain Severity Among Individuals with Osteoarthritis. Pain Manag Nurs 2023; 24:e97-e101. [PMID: 37544788 DOI: 10.1016/j.pmn.2023.07.005] [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: 11/22/2022] [Revised: 07/11/2023] [Accepted: 07/15/2023] [Indexed: 08/08/2023]
Abstract
Previous studies have reported an association between hypertension (HTN) and osteoarthritis (OA). However, limited research has examined the association between HTN and symptoms, such as pain severity, in people with OA. Therefore, the aim was to investigate the prevalence of HTN in individuals with OA and the association between HTN and pain severity in this population. This study was cross-sectional and included participants aged 50 years and older from the community. Demographic data were included and self-reported history of chronic illnesses including diabetes, HTN, cardiovascular disease, dyslipidemia, anemia, osteoporosis, neurological disease, and back pain were obtained. Numerous medications and chronic diseases were included. A subsample of people who self-reported osteoarthritis was included in this study. Pain severity was measured over the past 7 days using a pain numeric rating scale. Multiple linear regression was used after adjusting for covariates. A total of 82 participants with OA were included, and the prevalence of HTN among individuals with OA was 28.91%. Hypertension was significantly associated with increased joint pain severity in this population after adjustments for covariates (B=1.81; 95% CI, 0.65, 2.97; p = .003). Hypertension is prevalent in individuals with OA and is significantly associated with pain severity in this population. Future research should consider the effect of HTN control and medication on symptoms in people with OA. Clinicians may implement screening for HTN among individuals with OA because of the association between HTN and symptoms, such as pain, in this population.
Collapse
Affiliation(s)
- Aqeel M Alenazi
- Department of Health and Rehabilitation Sciences, Prince Sattam Bin Abdulaziz University, Alkharj, Riyadh, Saudi Arabia.
| | - Khalid M Alkhathami
- Department of Health Rehabilitation, Shaqra University, Shaqra, Riyadh, Saudi Arabia
| |
Collapse
|
|
12
|
Lopez J, Al-Nakkash L, Broderick TL, Castro M, Tobin B, Plochocki JH. Genistein Suppresses IL-6 and MMP-13 to Attenuate Osteoarthritis in Obese Diabetic Mice. Metabolites 2023; 13:1014. [PMID: 37755294 PMCID: PMC10534591 DOI: 10.3390/metabo13091014] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/24/2023] [Revised: 09/07/2023] [Accepted: 09/12/2023] [Indexed: 09/28/2023] Open
Abstract
Type 2 diabetes mellitus and osteoarthritis (OA) often present as comorbidities. We examined the role of plasma IL-6, chondrocyte MMP-13, and col10a expression in the development of OA in obese diabetic mice. We further investigated dietary genistein and exercise training as potential mitigators of OA. One hundred adult mice (50 females, 50 males) aged 6 weeks were randomized into 5 groups, including lean controls, obese diabetic controls, and obese diabetic mice treated with genistein, exercise training, and genistein plus exercise training. The obese diabetic state was induced by feeding the mice a high-fat, high-sugar diet. Genistein was incorporated into the diet at a concentration of 600 mg genistein/kg. Exercise training was performed on a treadmill and consisted of daily 30 min sessions at 12 m/min, 5 days/week for a 12-week period. After treatment, plasma was collected, and proximal tibias were removed for analysis. Plasma IL-6 and MMP-13 were elevated while col10a was reduced in obese diabetic mice in comparison to lean controls. Dietary genistein treatment reduced IL-6 and MMP-13 expression and increased col10a expression. Histological examination of articular cartilage showed reduced thickness of the uncalcified zones and proteoglycan content in the cartilage of diabetic mice in comparison to mice fed genistein. Exercise training had no significant effect. In conclusion, genistein (and not exercise training) attenuates OA by reducing IL-6 and MMP-13 expression in diabetic mice.
Collapse
Affiliation(s)
- Janelle Lopez
- Arizona College of Osteopathic Medicine, Midwestern University, Glendale, AZ 85308, USA
| | - Layla Al-Nakkash
- Department of Physiology, College of Graduate Studies, Midwestern University, Glendale, AZ 85308, USA;
| | - Tom L. Broderick
- Laboratory of Diabetes and Exercise Metabolism, Department of Physiology, College of Graduate Studies, Midwestern University, Glendale, AZ 85308, USA;
| | - Monica Castro
- Department of Anatomy, College of Graduate Studies, Midwestern University, Glendale, AZ 85308, USA
| | - Brielle Tobin
- Arizona College of Osteopathic Medicine, Midwestern University, Glendale, AZ 85308, USA
| | - Jeffrey H. Plochocki
- Department of Anatomy, College of Graduate Studies, Midwestern University, Glendale, AZ 85308, USA
- College of Medicine, University of Central Florida, Orlando, FL 32827, USA
| |
Collapse
|
|
13
|
Herrero-Manley L, Alabajos-Cea A, Suso-Martí L, Cuenca-Martínez F, Calatayud J, Casaña J, Viosca-Herrero E, Vázquez-Arce I, Ferrer-Sargues FJ, Blanco-Díaz M. Serum lipid biomarkers and inflammatory cytokines associated with onset and clinical status of patients with early knee osteoarthritis. Front Nutr 2023; 10:1126796. [PMID: 37006936 PMCID: PMC10050464 DOI: 10.3389/fnut.2023.1126796] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2022] [Accepted: 02/24/2023] [Indexed: 03/17/2023] Open
Abstract
IntroductionOsteoarthritis (OA) is a common joint condition and one of the greatest causes of disability worldwide. The role of serum lipid and inflammatory biomarkers in the origin and development of the disease is not clear, although it could have important implications for diagnosis and treatment. The primary aim of this study was to evaluate differences of serum lipid and inflammatory biomarkers with knee EOA in comparison with matched controls, in order to determine the role of these factors in the origin of EOA.MethodsFor this proposal, a cross-sectional study with a non-randomized sample was performed. 48 subjects with early osteoarthritis (EOA) and 48 matched controls were selected and serum lipid levels (total cholesterol, LDL, HDL) and inflammatory biomarkers C-reactive protein (CRP), uric acid (UA) were analyzed. In addition, clinical (pain, disability) and functional (gait speed, sit-to-stand) variables were measured to establish their relationship to serum lipid levels and inflammatory biomarkers.ResultsPatients with EOA showed higher levels of total cholesterol LDL, UA, and CRP. Higher levels of total cholesterol, LDL and CRP were correlated with higher levels of pain intensity and higher disability (p < 0.05). In addition, UA and CRP were inversely correlated with gait speed and sit-to-stand tests (r = −0.038 to −0.5, p < 0.05).ConclusionThese results highlight the relevance of metabolic and proinflammatory aspects in the early stages of knee OA and could be key to developing early diagnoses to prevent the onset and development of the disease.
Collapse
Affiliation(s)
- Luz Herrero-Manley
- Servicio de Medicina Física y Rehabilitación, Hospital La Fe, Valencia, Spain
| | - Ana Alabajos-Cea
- Servicio de Medicina Física y Rehabilitación, Hospital La Fe, Valencia, Spain
- Grupo de Investigación en Medicina Física y Rehabilitación, Instituto de Investigación Sanitaria La Fe (IISLAFE), Valencia, Spain
| | - Luis Suso-Martí
- Exercise Intervention for Health Research Group (EXINH-RG), Department of Physiotherapy, University of Valencia, Valencia, Spain
| | | | - Joaquín Calatayud
- Exercise Intervention for Health Research Group (EXINH-RG), Department of Physiotherapy, University of Valencia, Valencia, Spain
- *Correspondence: Joaquín Calatayud,
| | - José Casaña
- Exercise Intervention for Health Research Group (EXINH-RG), Department of Physiotherapy, University of Valencia, Valencia, Spain
| | | | - Isabel Vázquez-Arce
- Servicio de Medicina Física y Rehabilitación, Hospital La Fe, Valencia, Spain
| | | | - María Blanco-Díaz
- Department of Surgery and Medical Surgical Specialties, Faculty of Medicine and Health Sciences, University of Oviedo, Oviedo, Spain
| |
Collapse
|
|
14
|
Arce-Rosas JI, González-Hernández LA, Cabrera-Silva RI, Alvarez-Zavala M, Sánchez-Reyes K, Tafoya Arreguín GA, Martinez Ruíz JDJ, Cerda de la Torre R, Ramos-Solano M, Andrade-Villanueva JF. Ghrelin level as a biomarker for knee osteoarthritis severity and appearance in HIV + patients. Knee 2022; 39:100-105. [PMID: 36182829 DOI: 10.1016/j.knee.2022.08.005] [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: 02/04/2022] [Revised: 07/01/2022] [Accepted: 08/12/2022] [Indexed: 02/02/2023]
Abstract
BACKGROUND Knee Osteoarthritis (KOA) is a multifactorial disease with several mechanisms to promote articular cartilage damage. New molecules, such as ghrelin, have been recently reported to participate in the pathogenesis and progression of KOA. In HIV + patients, arthralgias are the most frequent musculoskeletal manifestations, mainly affecting joints such as the knee. Also, it has been reported that HIV + patients have a reduction of ghrelin even with treatment compared to HIV- patients. However, there is no report in the literature evaluating ghrelin and KOA in the HIV + population. We aimed to evaluate whether serum ghrelin levels can function as a biomarker for OA in HIV + patients. METHODS We recruited 40 patients, 20 HIV+, and 20 HIV- controls, and grouped as follows: HIV+/KOA+; HIV+/KOA-; HIV-/KOA+; HIV-/KOA-. Clinical features were obtained during clinical visits. Peripheral blood samples were acquired to measure serum ghrelin levels. RESULTS The HIV+/KOA + group significantly reduced serum ghrelin levels when compared with the other groups. Comparing the ghrelin levels with the patients' nadir of CD4+ T-cells count, we identified a statistically significant negative correlation in the KOA- group (r = -0.80, P < 0.007). An ROC curve analysis, for the accuracy of ghrelin levels to identified HIV+/KOA + from HIV+/KOA- patients, found an area under the curve of 0.83 (95 % CI 0.65-0.10; P = 0.017), with a cut-off < 4026 pg/mL serum ghrelin levels, with a sensitivity of 0.62 (95 % CI 0.32-0.86), and a specificity of 0.10 (95 % CI 0.59-0.10). CONCLUSION This study shows the potential use of ghrelin levels as a biomarker for KOA in the high-risk HIV population that should be further analyzed.
Collapse
Affiliation(s)
- Jorge I Arce-Rosas
- Servicio de Traumatología y Ortopedia, Hospital Civil de Guadalajara 'Fray Antonio Alcalde', Guadalajara, Jalisco, Mexico
| | - Luz A González-Hernández
- Unidad de VIH, Hospital Civil de Guadalajara 'Fray Antonio Alcalde', Guadalajara, Jalisco, Mexico; Universidad de Guadalajara, Instituto de Investigación en Inmunodeficiencias y VIH (InIVIH), Centro Universitario de Ciencias de la Salud, Guadalajara, Jalisco, Mexico
| | - Rodolfo I Cabrera-Silva
- Universidad de Guadalajara, Instituto de Investigación en Inmunodeficiencias y VIH (InIVIH), Centro Universitario de Ciencias de la Salud, Guadalajara, Jalisco, Mexico
| | - Monserrat Alvarez-Zavala
- Universidad de Guadalajara, Instituto de Investigación en Inmunodeficiencias y VIH (InIVIH), Centro Universitario de Ciencias de la Salud, Guadalajara, Jalisco, Mexico
| | - Karina Sánchez-Reyes
- Universidad de Guadalajara, Instituto de Investigación en Inmunodeficiencias y VIH (InIVIH), Centro Universitario de Ciencias de la Salud, Guadalajara, Jalisco, Mexico
| | - Gustavo A Tafoya Arreguín
- Servicio de Traumatología y Ortopedia, Hospital Civil de Guadalajara 'Fray Antonio Alcalde', Guadalajara, Jalisco, Mexico
| | - Jose de Jesús Martinez Ruíz
- Servicio de Traumatología y Ortopedia, Hospital Civil de Guadalajara 'Fray Antonio Alcalde', Guadalajara, Jalisco, Mexico
| | - Rodrigo Cerda de la Torre
- Servicio de Radiología e Imagen, Hospital Civil de Guadalajara 'Fray Antonio Alcalde', Guadalajara, Jalisco, Mexico
| | - Moisés Ramos-Solano
- Universidad de Guadalajara, Instituto de Investigación en Inmunodeficiencias y VIH (InIVIH), Centro Universitario de Ciencias de la Salud, Guadalajara, Jalisco, Mexico
| | - Jaime F Andrade-Villanueva
- Unidad de VIH, Hospital Civil de Guadalajara 'Fray Antonio Alcalde', Guadalajara, Jalisco, Mexico; Universidad de Guadalajara, Instituto de Investigación en Inmunodeficiencias y VIH (InIVIH), Centro Universitario de Ciencias de la Salud, Guadalajara, Jalisco, Mexico.
| |
Collapse
|
|
15
|
Terkawi MA, Ebata T, Yokota S, Takahashi D, Endo T, Matsumae G, Shimizu T, Kadoya K, Iwasaki N. Low-Grade Inflammation in the Pathogenesis of Osteoarthritis: Cellular and Molecular Mechanisms and Strategies for Future Therapeutic Intervention. Biomedicines 2022; 10:biomedicines10051109. [PMID: 35625846 PMCID: PMC9139060 DOI: 10.3390/biomedicines10051109] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2022] [Revised: 05/06/2022] [Accepted: 05/08/2022] [Indexed: 01/15/2023] Open
Abstract
Osteoarthritis (OA) is a musculoskeletal disease characterized by cartilage degeneration and stiffness, with chronic pain in the affected joint. It has been proposed that OA progression is associated with the development of low-grade inflammation (LGI) in the joint. In support of this principle, LGI is now recognized as the major contributor to the pathogenesis of obesity, aging, and metabolic syndromes, which have been documented as among the most significant risk factors for developing OA. These discoveries have led to a new definition of the disease, and OA has recently been recognized as a low-grade inflammatory disease of the joint. Damage-associated molecular patterns (DAMPs)/alarmin molecules, the major cellular components that facilitate the interplay between cells in the cartilage and synovium, activate various molecular pathways involved in the initiation and maintenance of LGI in the joint, which, in turn, drives OA progression. A better understanding of the pathological mechanisms initiated by LGI in the joint represents a decisive step toward discovering therapeutic strategies for the treatment of OA. Recent findings and discoveries regarding the involvement of LGI mediated by DAMPs in OA pathogenesis are discussed. Modulating communication between cells in the joint to decrease inflammation represents an attractive approach for the treatment of OA.
Collapse
|
|
16
|
Zeng Z, Dai Y, Deng S, Zou S, Dou T, Wei F. Synovial mesenchymal stem cell-derived extracellular vesicles alleviate chondrocyte damage during osteoarthritis through microRNA-130b-3p-mediated inhibition of the LRP12/AKT/β-catenin axis. Immunopharmacol Immunotoxicol 2022; 44:247-260. [PMID: 35174753 DOI: 10.1080/08923973.2022.2038192] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
Abstract
BACKGROUND Synovial mesenchymal stem cells (SMSCs) have been discussed as promising tools for protecting chondrocytes from loss and inhibiting osteoarthritis (OA). This work infocuses on the function of SMSC-derived extracellular vesicles (EVs) in chondrocytes during OA and the molecular mechanism. METHODS EVs were extracted from SMSCs and identified. Chondrocytes were treated with interleukin (IL)-1β to induce an OA-like condition in vitro and then treated with EVs. The proliferation, apoptosis, migration, extracellular matrix (ECM) degradation and inflammation in chondrocytes were examined. Key microRNAs (miRNAs) carried by EVs were screened using a microarray analysis, and the downstream molecules involved were explored using bioinformatic analysis. Rescue experiments were performed to validate the involvements of these molecules in EV-mediated events. RESULTS EVs restored proliferation and migration while reduced apoptosis, ECM degradation and the secretion of pro-inflammatory cytokines in chondrocytes induced by IL-1β. miR-130b-3p was significantly elevated in chondrocytes after EVs treatment. Knockdown of miR-130b-3p blocked the protective roles of EVs against IL-1β-induced damage to chondrocytes. miR-130b-3p was found to target LDL receptor related protein 12 (LRP12) mRNA in chondrocytes. Overexpression of LRP12 counteracted the effects of EVs as well and activated the AKT/β-catenin signaling pathway. CONCLUSION This study provided evidence that EVs alleviate chondrocyte damage during OA through miR-130b-3p-mediated inhibition of the LRP12/AKT/β-catenin axis. This study may offer novel thoughts into the protection of chondrocytes and the management of OA.
Collapse
Affiliation(s)
- Zhenhua Zeng
- Department of Pain, the First People's Hospital of Jiashan County, Jiaxing, Zhejiang, P.R. China
| | - Yi Dai
- Department of Pain, the First People's Hospital of Jiashan County, Jiaxing, Zhejiang, P.R. China
| | - Shuo Deng
- Department of Pain, the First People's Hospital of Jiashan County, Jiaxing, Zhejiang, P.R. China
| | - Sanbao Zou
- Department of Pain, the First People's Hospital of Jiashan County, Jiaxing, Zhejiang, P.R. China
| | - Tingyang Dou
- Department of Pain, the First People's Hospital of Jiashan County, Jiaxing, Zhejiang, P.R. China
| | - Feng Wei
- Department of Pain, the First People's Hospital of Jiashan County, Jiaxing, Zhejiang, P.R. China
| |
Collapse
|
|
17
|
Erceg-Rukavina T, Dragičević-Cvjetković D, Đuric D, Stojiljković M, Škrbić R. The effect of sulphate-sulphide mineral baths on blood glucose level in patients with knee osteoarthritis. SCRIPTA MEDICA 2022. [DOI: 10.5937/scriptamed53-41890] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/08/2023] Open
Abstract
Background/Aim: Type 2 diabetes is a common comorbidity in patients with knee osteoarthritis. Bearing in mind that obesity and insulin resistance are risk factors for the development of knee osteoarthritis, physical therapy and balneotherapy containing hydrogen sulphide (H2S) has a positive effect on the functional and metabolic status of these patients. This work was aimed to investigate the effect of sulphate-sulphide-rich mineral baths containing H2S on the level of serum glucose in patients with knee osteoarthritis. Methods: An open prospective randomised clinical trial included patients suffering from stage I and II of the knee osteoarthritis. Patients were divided into two groups of 40 subjects each: control group and experimental group. All subjects underwent inpatient physical treatment consisting of kinesitherapy and transcutaneous electrical nerve stimulation (TENS) 6 days a week. Patients from experimental group, in addition to all the mentioned treatments, also took sulphate-sulphide mineral water baths once a day for 30 minutes for 7 days, unlike the patients from control group who took tap water baths, according to the same schedule. The level of serum glucose was monitored in all patients on admission, after discharge and 6 months after the treatment. The Student t-test was used for statistical data processing and p < 0.05 was considered as statistically significant. Results: Study included 80 patients of both sexes, with an average age of 67.00 ± 5.75 years. All patients had elevated serum glucose values on admission. The initial levels of glycaemia in the control and experimental groups were not significantly different (6.99 ± 1.95 and 7.88 ± 1.90 mmol/L, respectively). At discharge, patients who performed balneotherapy had a statistically significant decrease in serum glucose values compared to patients from the control group (by 1.84 vs 0.26 mmol/L, p < 0.001). This effect did not persist six months after the end of the treatment (p > 0.05). Conclusion: The application of balneotherapy with sulphate-sulphide mineral baths containing H2S as a potent gas transmitter significantly reduces serum glucose levels in patients with knee osteoarthritis.
Collapse
|
|
18
|
Shi X, Schlenk EA. Association of Hypertension with Knee Pain Severity Among People with Knee Osteoarthritis. Pain Manag Nurs 2021; 23:135-141. [PMID: 34474997 DOI: 10.1016/j.pmn.2021.08.002] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/21/2021] [Revised: 07/26/2021] [Accepted: 08/02/2021] [Indexed: 01/21/2023]
Abstract
PURPOSE To examine the association of hypertension with knee pain severity in individuals with knee osteoarthritis (OA). DESIGN Cross-sectional study of baseline data collected by the Osteoarthritis Initiative. METHODS Participants with knee OA (N=1,363) were categorized into four groups based on blood pressure (BP): 1) systolic < 120 mm HG and diastolic < 80 mm Hg; 2) 120 ≤ systolic < 130 mm Hg and diastolic < 80 mm Hg; 3) 130 ≤ systolic < 140 mm Hg or 80 ≤ diastolic < 90 mm Hg; 4) systolic ≥ 140 mm Hg or diastolic ≥ 90 mm Hg. OA knee pain severity was measured by Pain subscale of Western Ontario and McMaster Universities Osteoarthritis Index in the past 48 hours, Pain subscale of Knee Injury and Osteoarthritis Outcome Score (KOOS) in the past 7 days, and numeric rating scale (NRS) in the past 30 days. Linear regression was used to examine the relationship between hypertension and knee pain severity. RESULTS Compared with the normal BP group, individuals with stage 2 hypertension reported significantly higher OA knee pain severity by KOOS in the past 7 days (β=-2.05 [95% CI -4.09, -0.01], p=0.049) and by NRS in the past 30 days (β=0.31 [95% CI 0.01, 0.62], p=0.045) after adjustments for demographic and medical factors. CONCLUSIONS Hypertension was associated with higher OA knee pain severity in individuals with knee OA. CLINICAL IMPLICATIONS Nurses can recommend adjunctive non-pharmacological treatments and adherence strategies to help control hypertension, which may help decrease OA knee pain.
Collapse
Affiliation(s)
- Xiaojun Shi
- University of Pittsburgh School of Nursing, 3500 Victoria Street, Room 415, Pittsburgh, PA 15261, USA.
| | - Elizabeth A Schlenk
- University of Pittsburgh School of Nursing, 3500 Victoria Street, Room 415, Pittsburgh, PA 15261, USA.
| |
Collapse
|
|
19
|
Association of the Risk of Osteoarthritis and Hypertension in the Korean Adult Population Aged 40-59 in Pre- and Postmenopausal Women: Using Korea National Health and Nutrition Examination Survey 2012-2016 Data. Int J Hypertens 2021; 2021:8065838. [PMID: 33708440 PMCID: PMC7929687 DOI: 10.1155/2021/8065838] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/25/2020] [Revised: 01/12/2021] [Accepted: 02/17/2021] [Indexed: 12/20/2022] Open
Abstract
Purpose Previous studies reported the relation of osteoarthritis (OA) and hypertension (HTN) mostly in postmenopausal women. This study aimed to identify the association between OA and HTN in pre- and postmenopausal women. Methods We used data of 4,627 middle-aged (40–59 years) women from the Korea National Health and Nutrition Examination Survey (KNHANES) from 2012 to 2016. Chi-square and t-test compared the characteristics of the participants. Binomial logistic regression was used to identify an association between OA and HTN under controlling covariates such as age, tobacco smoking, alcohol consumption, and obesity. Results There were 1,859 participants with non-OA and menopause, 104 with OA and nonmenopause, and 375 with OA and menopause, respectively. The number of women with OA and HTN was 129. OA was significantly associated with HTN diagnosis in postmenopausal women under controlling covariates (odds ratio: 1.408, 95% CI: 1.092–1.815, p=0.008). However, this relationship was weakened in premenopausal women (odds ratio: 1.651, 95% CI: 0.950–2.869, p=0.075). Conclusion In conclusion, women with HTN showed a distinct association with OA than the normotensives, and this relationship was more apparent among postmenopausal women. Further research is needed for a preventive approach.
Collapse
|
|
20
|
He H, Lu M, Shi H, Yue G, Luo H. Vaspin regulated cartilage cholesterol metabolism through miR155/LXRα and participated in the occurrence of osteoarthritis in rats. Life Sci 2021; 269:119096. [PMID: 33482192 DOI: 10.1016/j.lfs.2021.119096] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/07/2020] [Revised: 12/28/2020] [Accepted: 01/11/2021] [Indexed: 01/16/2023]
Abstract
AIMS This study intends to explore the role of Vaspin and cholesterol metabolism in the process of osteoarthritis (OA) and its mechanism in vitro and in vivo. MAIN METHODS In vitro, chondrocytes were treated with interleukin-1β (IL-1β, 20 ng/mL) in combination with Vaspin at different concentrations for 48 h. The expressions of Aggrecan (ACAN), Collagen 2a1 (Col2a1), A Disintegrin And Metalloproteinase with Thrombo Spondin type 1 motifs 5 (ADAMTS 5), and Matrix metalloproteinase 13 (MMP13) were detected. In vivo, the expression of liver X receptor (LXRα) and other Cholesterol efflux related genes were detected in the rat OA knee cartilage-induced by papain. KEY FINDINGS In vitro, in a concentration-dependent manner, Vaspin reversed the decreased expression of ACAN and Col2a1, and the increased expression of ADAMTS 5 and MMP13 caused by IL-1β. Besides, Vaspin promoted the expression of LXRα and other Cholesterol efflux related genes in a concentration-dependent manner in chondrocytes. However, miR155 mimics reversed the Vaspin-induced expression changes of cholesterol efflux pathway in chondrocytes. In vivo, the expression of LXRα and other Cholesterol efflux related genes were decreased in the rat OA knee cartilage-induced by papain. Besides, the level of Vaspin was reduced and the miroRNA155 (miR155) expression was increased in OA knee cartilage of rats. SIGNIFICANCE In conclusion, the decreased expression of Vaspin inhibited the expression of Cholesterol efflux pathway via miR155/LXRα. Finally, the inhibited Cholesterol efflux pathway led to the cholesterol accumulation and OA in cartilage.
Collapse
Affiliation(s)
- Hangyuan He
- Department of Joint Osteopathy, Guangxi Liuzhou Workers Hospital, The Fourth Affiliated Hospital of Guangxi Medical University, Liuzhou, Guangxi 545000, China; Department of Orthopedic Surgery, Zhongnan Hospital of Wuhan University, Wuhan 430071, China
| | - Mengting Lu
- Department of Joint Osteopathy, Guangxi Liuzhou Workers Hospital, The Fourth Affiliated Hospital of Guangxi Medical University, Liuzhou, Guangxi 545000, China
| | - Huasong Shi
- Department of Orthopedic Surgery, Zhongnan Hospital of Wuhan University, Wuhan 430071, China
| | - Guoping Yue
- Department of Joint Osteopathy, Guangxi Liuzhou Workers Hospital, The Fourth Affiliated Hospital of Guangxi Medical University, Liuzhou, Guangxi 545000, China
| | - Hanwen Luo
- Department of Joint Osteopathy, Guangxi Liuzhou Workers Hospital, The Fourth Affiliated Hospital of Guangxi Medical University, Liuzhou, Guangxi 545000, China.
| |
Collapse
|
|
21
|
Erceg-Rukavina T, Dragičević-Cvjetković D. Lipid-reducing effects of sulphate-sulphide mineral water in patients with knee osteoarthritis. SCRIPTA MEDICA 2021. [DOI: 10.5937/scriptamed52-35248] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/02/2022] Open
Abstract
Background/Aim: The positive effect of thermal mineral waters on human health has been known for a long time. Many pathophysiological mechanisms of action of balneotherapy are not specified. Patients with gonarthrosis often have elevated values of serum lipids. This study aimed to examine the effect of drinking sulphate-sulphide thermo mineral water on the lipid status of patients with gonarthrosis. Methods: A prospective clinical study followed 60 patients, both sexes, mean age 65.02 ± 1.03, with gonarthrosis. All inpatient underwent physical treatment with topical application of sulphate-sulphide mineral water. Patients of group A (N = 30) had the use of this mineral water as an additional therapy by drinking, unlike patients of group B (N = 30) who drank plain water. The level of serum lipids of these patients was monitored at admission and 4 weeks after. The variance analysis test (ANOVA) with a level of statistical significance p < 0.001 was used for statistical analysis. Results: A significant reduction in the levels of all lipid fractions in the serum of patients with gonarthrosis was found 4 weeks after the completion of inpatient physical treatment in both study groups. This decrease was statistically significant in patients of group A (p < 0.001). Conclusion: Drinking sulphate-sulphide mineral water in patients with gonarthrosis shows a positive effect on the reduction of serum lipid levels in the short-term follow-up period.
Collapse
|
|
22
|
Park HM, Lee JH, Lee YJ. Positive Association of Serum Alkaline Phosphatase Level with Severe Knee Osteoarthritis: A Nationwide Population-Based Study. Diagnostics (Basel) 2020; 10:diagnostics10121016. [PMID: 33261160 PMCID: PMC7760969 DOI: 10.3390/diagnostics10121016] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2020] [Revised: 11/20/2020] [Accepted: 11/24/2020] [Indexed: 12/14/2022] Open
Abstract
Serum alkaline phosphatase (ALP), a well-known marker of hepatobiliary and bone disorders, has recently been discovered to be a biochemical marker of cardiometabolic diseases and chronic low-grade inflammation. We aimed to evaluate the association of serum ALP level with knee osteoarthritis in the general population. The study included 3060 men and women aged ≥50 years who participated in the 2009–2011 Korea National Health and Nutrition Examination Survey. The participants were categorized into three groups based on log-transformed serum ALP level as follows: T1 (1.74–2.32), T2 (2.33–2.43), and T3 (2.44–3.01). Their radiographs were evaluated by two well-trained radiologists using the Kellgren–Lawrence (KL) grading system. After excluding those with KL Grade 0, we categorized the remaining participants into two groups, a severe osteoarthritis group (KL Grade 4) and a non-severe osteoarthritis group (KL Grades 1 to 3). The odds ratios (ORs) with 95% confidence intervals (CIs) of severe osteoarthritis according to the tertiles of log-transformed serum ALP levels of patients with osteoarthritis were calculated using a weighted multivariate logistic regression analysis. Compared with T1, the adjusted ORs (95% CIs) for severe osteoarthritis of the T3 serum ALP group was 1.613 (1.087–2.394; p = 0.018) after adjusting for the confounding variables. Conclusively, serum ALP activity was independently and positively associated with severe knee osteoarthritis in middle-aged and older adults.
Collapse
Affiliation(s)
- Hye-Min Park
- Department of Family Medicine, Yonsei University College of Medicine, 211 Eonju-ro, Gangnam-gu, Seoul 06273, Korea;
- Department of Medicine, Graduate School, Yonsei University, 50-1 Yonsei-ro, Seodaemoon-gu, Seoul 03722, Korea;
| | - Jun-Hyuk Lee
- Department of Medicine, Graduate School, Yonsei University, 50-1 Yonsei-ro, Seodaemoon-gu, Seoul 03722, Korea;
- Department of Family Medicine, Yongin Severance Hospital, Yonsei University College of Medicine, 363 Dongbaekjukjeon-daero, Giheung-gu, Yongin-si, Gyeonggi-do 16995, Korea
| | - Yong-Jae Lee
- Department of Family Medicine, Yonsei University College of Medicine, 211 Eonju-ro, Gangnam-gu, Seoul 06273, Korea;
- Correspondence: ; Tel.: +82-2-2019-3481
| |
Collapse
|
|
23
|
Kim HS, Park HM, Kim H, Lee YJ. Association between the severity of periodontitis and osteoarthritis in middle-aged and older patients with type 2 diabetes: a nationwide population-based study. Arthritis Care Res (Hoboken) 2020; 74:403-409. [PMID: 33044789 DOI: 10.1002/acr.24484] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2020] [Revised: 08/19/2020] [Accepted: 10/06/2020] [Indexed: 11/11/2022]
Abstract
OBJECTIVE Periodontitis and osteoarthritis are major public health concerns that result in decreased quality of life among middle-aged and older adults. We sought to examine whether the severity of periodontitis is related to osteoarthritis according to the presence of type 2 diabetes. METHODS This study included 3,527 participants aged ≥50 years from the Korean National Health and Nutrition Examination Survey. Periodontitis was assessed using the Community Periodontal Index; severe periodontitis was defined as periodontal tissue forming deep periodontal pockets ≥6 mm depth. Osteoarthritis was defined as Kellgren-Lawrence grade ≥2 on radiographic images of the knee or hip area with joint pain. The odds ratios (ORs) and 95% confidence intervals (CIs) for osteoarthritis according to the severity of periodontitis, stratified by type 2 diabetes, were calculated using multiple logistic regression analyses. RESULTS Participants with type 2 diabetes were more likely to have osteoarthritis as the severity of periodontitis increased (nonsevere periodontitis: 1.23 [0.67-2.32]; severe periodontitis: 3.01 [1.51-5.84]) after adjusting for age, sex, body mass index, smoking status, alcohol consumption, regular exercise, education level, household income, hypertension, and frequent tooth-brushing. However, this positive association was not found in individuals without type 2 diabetes after adjusting for the same co-variables. CONCLUSIONS Severe periodontitis was positively and significantly associated with osteoarthritis in middle-aged and older individuals with type 2 diabetes. Our findings suggest that the oral inflammation manifesting in periodontitis may be at least partly involved in the pathogenesis of osteoarthritis, particularly in patients with type 2 diabetes.
Collapse
Affiliation(s)
- Hyoung-Sik Kim
- Department of Orthopedic Surgery, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Hye-Min Park
- Department of Family Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea.,Department of Medicine, Graduate School of Medicine, Yonsei University, Seoul, Republic of Korea
| | - Haeyoung Kim
- Department of Integrative Medicine, Major in Digital Healthcare, Yonsei University College of Medicine, Seodaemun-gu, Korea (the Republic of)
| | - Yong-Jae Lee
- Department of Family Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea
| |
Collapse
|
|
24
|
He J, Yang H, Xu Z, Li J, Chen G, Jiang L, Wu L, Zhou X. A functional polymorphism in the paired basic amino acid-cleaving enzyme 4 gene confers osteoarthritis risk in a population of Eastern China. Genet Mol Biol 2020; 43:e20190115. [PMID: 32167127 PMCID: PMC7197988 DOI: 10.1590/1678-4685-gmb-2019-0115] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/19/2019] [Accepted: 11/19/2019] [Indexed: 01/01/2023] Open
Abstract
Paired basic amino acid-cleaving enzyme 4 (PACE4), a proprotein convertase, is
involved in the activation of aggrecanases (ADAMTS-4 and ADAMTS-5) in
osteoarthritic and cytokine-stimulated cartilage. Activated aggrecanases cause
aggrecan degradation and thus, contribute to osteoarthritis (OA). In this study,
we investigated the association between PACE4 gene
polymorphisms and OA risk. One single-nucleotide polymorphism (rs4965833) in the
PACE4 gene was genotyped in 432 OA patients and 523 healthy
controls using matrix-assisted laser desorption/ionization time-of-flight mass
spectrometry. Quantitative reverse transcription PCR (qRT-PCR) was used to
determine the relative expression of PACE4 in blood samples
from 90 OA patients (30 for each genotype). The relative expression level of
PACE4 mRNA was higher in the GG genotype as compared to the
AA/AG group. Moreover, the PACE4 rs4965833 polymorphism was
associated with increased risk of OA, especially among individuals aged ≥55
years and with a body mass index ≥25. There was no significant association
between the PACE4 rs4965833 polymorphism and clinical
parameters of OA patients, such as erythrocyte sedimentation rate, C-reactive
protein, Visual Analog Scale for pain and Lequesne’s index. In conclusion, the
rs4965833 polymorphism in the 3’-UTR of PACE4 is associated
with OA susceptibility.
Collapse
Affiliation(s)
- Jin He
- Department of Orthopedics, Jintan Hospital Affiliated to Jiangsu University, Changzhou, China
| | - Haoyu Yang
- Department of Orthopedics, Wuxi No.9 People's Hospital Affiliated to Soochow University, Wuxi, Jiangsu, China
| | - Zhonghua Xu
- Department of Orthopedics, Jintan Hospital Affiliated to Jiangsu University, Changzhou, China
| | - Jin Li
- Department of Orthopedic Surgery, the Second Affiliated Hospital of Jiaxing University, Jiaxing, China
| | - Gang Chen
- Department of Orthopedic Surgery, the Second Affiliated Hospital of Jiaxing University, Jiaxing, China
| | - Lifeng Jiang
- Department of Orthopedic Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Lidong Wu
- Department of Orthopedic Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Xindie Zhou
- Department of Orthopedics, The Affiliated Changzhou No.2 People's Hospital of Nanjing Medical University, Changzhou, China
| |
Collapse
|
|
25
|
Cheng S, Peng L, Xu B, Chen W, Chen Y, Gu Y. Protective Effects of Hydrogen-Rich Water Against Cartilage Damage in a Rat Model of Osteoarthritis by Inhibiting Oxidative Stress, Matrix Catabolism, and Apoptosis. Med Sci Monit 2020; 26:e920211. [PMID: 31927559 PMCID: PMC6977642 DOI: 10.12659/msm.920211] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022] Open
Abstract
Background The aim of this study was to investigate the mechanisms underlying the potential effects of hydrogen-rich water (HW) on articular cartilage in a rat osteoarthritis (OA) model. Material/Methods A rat model of OA was established using the modified Hulth method, and rats were forced to exercise for 30 min every day 1 week after surgery for 7 weeks. Mankin’s method was used to score the severity of OA. The animals were assigned into the OA group, OA+HW group, and sham operation group. After 8 weeks, the animals in the OA group had a Mankin score >8 points, and HW was administered into the knee joint. After 2 weeks of treatment, articular cartilage was obtained for pathological examination, consisting of hematoxylin and eosin, toluidine blue, and Hoechst staining, as well as quantitative real-time PCR and Western blot analyses. This combination of pharmacological and molecular biological analyses was performed to examine the mechanism underlying the protective effect of HW on articular cartilage. Results The antioxidant effects of HW suppressed oxidative damage, which may have aided the inhibition of ECM-degrading enzymes (MMP3, MMP13, ADAMT4, and ADAMT5), the upregulation of Col II and aggrecan expression, and the downregulation of COX-2, iNOS, and NO expression. The results of HE staining indicated intra-articular treatment of HW attenuated cartilage degradation. However, Hoechst staining in the OA group indicated the nuclei of the fragmented chondrocytes were condensed compared to the sham operation group, and this effect was inhibited by HW. Conclusions HW showed a protective effect against the progression of OA in an animal model, which may have been mediated by its anti-oxidant and anti-apoptotic activities.
Collapse
Affiliation(s)
- ShaoWen Cheng
- Trauma Center, The First Affiliated Hospital of Hainan Medical College, Haikou, Hainan, China (mainland)
| | - Lei Peng
- Trauma Center, The First Affiliated Hospital of Hainan Medical College, Haikou, Hainan, China (mainland)
| | - BaiChao Xu
- Department of Orthopedic Surgery, The Second Affiliated Hospital of Hainan Medical College, Haikou, Hainan, China (mainland).,Hainan Medical College, Haikou, Hainan, China (mainland)
| | - WenSheng Chen
- Department of Orthopedic Surgery, The Second Affiliated Hospital of Hainan Medical College, Haikou, Hainan, China (mainland)
| | - YangPing Chen
- Trauma Center, The First Affiliated Hospital of Hainan Medical College, Haikou, Hainan, China (mainland)
| | - YunTao Gu
- Department of Orthopedic Surgery, The Second Affiliated Hospital of Hainan Medical College, Haikou, Hainan, China (mainland)
| |
Collapse
|
|
26
|
Sansone V, Applefield RC, De Luca P, Pecoraro V, Gianola S, Pascale W, Pascale V. Does a high-fat diet affect the development and progression of osteoarthritis in mice?: A systematic review. Bone Joint Res 2020; 8:582-592. [PMID: 31934329 PMCID: PMC6946912 DOI: 10.1302/2046-3758.812.bjr-2019-0038.r1] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/09/2022] Open
Abstract
Aims The aim of this study was to systematically review the literature for evidence of the effect of a high-fat diet (HFD) on the onset or progression of osteoarthritis (OA) in mice. Methods A literature search was performed in PubMed, Embase, Web of Science, and Scopus to find all studies on mice investigating the effects of HFD or Western-type diet on OA when compared with a control diet (CD). The primary outcome was the determination of cartilage loss and alteration. Secondary outcomes regarding local and systemic levels of proteins involved in inflammatory processes or cartilage metabolism were also examined when reported. Results In total, 14 publications met our inclusion criteria and were included in our review. Our meta-analysis showed that, when measured by the modified Mankin Histological-Histochemical Grading System, there was a significantly higher rate of OA in mice fed a HFD than in mice on a CD (standardized mean difference (SMD) 1.27, 95% confidence interval (CI) 0.63 to 1.91). Using the Osteoarthritis Research Society International (OARSI) score, there was a trend towards HFD causing OA (SMD 0.78, 95% CI -0.04 to 1.61). In terms of OA progression, a HFD consistently worsened the progression of surgically induced OA when compared with a CD. Finally, numerous inflammatory cytokines such as tumour necrosis factor alpha (TNF-α), interleukin (IL)-1β, and leptin, among others, were found to be altered by a HFD. Conclusion A HFD seems to induce or exacerbate the progression of OA in mice. The metabolic changes and systemic inflammation brought about by a HFD appear to be key players in the onset and progression of OA. Cite this article:Bone Joint Res 2019;8:582–592.
Collapse
Affiliation(s)
- Valerio Sansone
- Department of Orthopaedics, Universitá degli Studi di Milano and IRCCS Istituto Ortopedico Galeazzi, Milan, Italy
| | | | | | - Valentina Pecoraro
- Department of Laboratory Medicine, Ospedale Civile Sant'Agostino Estense di Baggiovra, Baggiovara, Italy
| | | | | | - Valerio Pascale
- Department of Orthopaedics, Universitá degli Studi di Milano and IRCCS Istituto Ortopedico Galeazzi, Milan, Italy
| |
Collapse
|
|
27
|
Xiao L, Lin S, Zhan F. The association between serum uric acid level and changes of MRI findings in knee osteoarthritis: A retrospective study (A STROBE-compliant article). Medicine (Baltimore) 2019; 98:e15819. [PMID: 31124983 PMCID: PMC6571402 DOI: 10.1097/md.0000000000015819] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/26/2022] Open
Abstract
The objective of this study was to examine whether Magnetic resonance imaging (MRI) features of knee osteoarthritis (OA) had an association with the level of serum uric acid (SUA). The MRI of the OA patients from June 2015 to July 2017 were studied. The patients fulfilled the following inclusion criteria: 1) meet American College of Rheumatology (ACR) radiological and clinical criteria for OA of the knee, 2) age ≤ 65years old, 3) Body mass index (BMI) < 25 kg/m. Patients with OA were categorized into two groups based on the level of SUA. Patients with SUA level lower than 360 umol/L were recruited into the first group and the others were the second group. Odds ratios (OR) and 95% confidence intervals (CI) for SUA level and different MRI patterns were estimated with multivariable logistic regression.71 patients were included in this research. The mean age of the first group was 54.5 ± 8.4 and the second group was 55.6 ± 6.4. The Body Mass Index (BMI) of two groups was 22.7 ± 1.3 and 23.23 ± 1.9 separately. The mean SUA and creatinine (CR) level of the second group were 433.8 ± 70.6 umol/L and 80.1 ± 23.9 umol/L. There were statistically more focal erosions, osteophytes, bone marrow lesions and synovitis in the MRIs of the second group. A positive association between SUA level and synovitis as well as soft tissue swelling in MRIs was observed in patients with knee OA (OR = 1.017; 1.008, 95% CI: 1.007-1.028; 1.000-1.016). In conclusion, subjects with higher SUA level were more likely to have MRI abnormalities. OA patients need to lower their SUA level in order to keep the disease from progressing.
Collapse
|
|
28
|
Chen IJ, Lin SH, Wong CS. Oral shea nut oil triterpene concentrate supplement ameliorates pain and histological assessment of articular cartilage deterioration in an ACLT injured rat knee osteoarthritis model. PLoS One 2019; 14:e0215812. [PMID: 31002699 PMCID: PMC6474620 DOI: 10.1371/journal.pone.0215812] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/07/2018] [Accepted: 04/09/2019] [Indexed: 01/25/2023] Open
Abstract
Osteoarthritis (OA) is a multifactorial joint disease and a common disabling condition in the elderly population. The associated pain and pathohistological changes in cartilage are common features of OA in both humans and animal models. Shea nut oil extract (SheaFlex75) contains a high triterpenoid concentration and has demonstrated anti-inflammatory and antiarthritic effects in both human and animal studies. In this study, we aim to investigate the potential of SheaFlex75 to prevent articular cartilage deterioration in a rat model of chronic OA progression. By employing anterior cruciate ligament transection (ACLT) with medial meniscectomy (MMx)-induced OA, we found attenuation of both early and chronic onset OA pain and cartilage degeneration in ACLT+MMx rats receiving SheaFlex75 dietary supplementation. Under long-term oral administration, the rats with induced OA presented sustained protection of both pain and OA cartilage integrity compared to the OA-control rats. Moreover, rats subjected to long-term SheaFlex75 ingestion showed normal biochemical profiles (AST, BUN and total cholesterol) and presented relatively lower triglycerides (TGs) and body weights than the OA-control rats, which suggested the safety of prolonged use of this oil extract. Based on the present evidence, preventive management is advised to delay/prevent onset and progression in OA patients. Therefore, we suggest that SheaFlex75 may be an effective management strategy for symptom relief and cartilage protection in patients with both acute and chronic OA.
Collapse
Affiliation(s)
- Ing-Jung Chen
- Department of Medical Research, Cathay General Hospital, Taipei, Taiwan
- Department of Anesthesiology, Cathay General Hospital, Taipei, Taiwan
| | - Sheng-Hsiung Lin
- Planing and Management Office, Tri-Service General Hospital, Taipei, Taiwan
| | - Chih-Shung Wong
- Department of Anesthesiology, Cathay General Hospital, Taipei, Taiwan
- Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei, Taiwan
- * E-mail:
| |
Collapse
|
|
29
|
Kozijn AE, Tartjiono MT, Ravipati S, van der Ham F, Barrett DA, Mastbergen SC, Korthagen NM, Lafeber FPJG, Zuurmond AM, Bobeldijk I, Weinans H, Stoop R. Human C-reactive protein aggravates osteoarthritis development in mice on a high-fat diet. Osteoarthritis Cartilage 2019; 27:118-128. [PMID: 30248505 DOI: 10.1016/j.joca.2018.09.007] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/22/2018] [Revised: 07/17/2018] [Accepted: 09/13/2018] [Indexed: 02/02/2023]
Abstract
OBJECTIVE C-reactive protein (CRP) levels can be elevated in osteoarthritis (OA) patients. In addition to indicating systemic inflammation, it is suggested that CRP itself can play a role in OA development. Obesity and metabolic syndrome are important risk factors for OA and also induce elevated CRP levels. Here we evaluated in a human CRP (hCRP)-transgenic mouse model whether CRP itself contributes to the development of 'metabolic' OA. DESIGN Metabolic OA was induced by feeding 12-week-old hCRP-transgenic males (hCRP-tg, n = 30) and wild-type littermates (n = 15) a 45 kcal% high-fat diet (HFD) for 38 weeks. Cartilage degradation, osteophytes and synovitis were graded on Safranin O-stained histological knee joint sections. Inflammatory status was assessed by plasma lipid profiling, flow cytometric analyses of blood immune cell populations and immunohistochemical staining of synovial macrophage subsets. RESULTS Male hCRP-tg mice showed aggravated OA severity and increased osteophytosis compared with their wild-type littermates. Both classical and non-classical monocytes showed increased expression of CCR2 and CD86 in hCRP-tg males. HFD-induced effects were evident for nearly all lipids measured and indicated a similar low-grade systemic inflammation for both genotypes. Synovitis scores and synovial macrophage subsets were similar in the two groups. CONCLUSIONS Human CRP expression in a background of HFD-induced metabolic dysfunction resulted in the aggravation of OA through increased cartilage degeneration and osteophytosis. Increased recruitment of classical and non-classical monocytes might be a mechanism of action through which CRP is involved in aggravating this process. These findings suggest interventions selectively directed against CRP activity could ameliorate metabolic OA development.
Collapse
Affiliation(s)
- A E Kozijn
- Metabolic Health Research, TNO, Leiden, the Netherlands; Department of Orthopaedics, University Medical Center (UMC) Utrecht, Utrecht University, Utrecht, The Netherlands; Department of Rheumatology & Clinical Immunology, UMC Utrecht, Utrecht University, Utrecht, The Netherlands
| | - M T Tartjiono
- Metabolic Health Research, TNO, Leiden, the Netherlands
| | - S Ravipati
- Centre for Analytical Bioscience, School of Pharmacy, University of Nottingham, Nottingham, United Kingdom
| | - F van der Ham
- Metabolic Health Research, TNO, Leiden, the Netherlands
| | - D A Barrett
- Centre for Analytical Bioscience, School of Pharmacy, University of Nottingham, Nottingham, United Kingdom
| | - S C Mastbergen
- Department of Rheumatology & Clinical Immunology, UMC Utrecht, Utrecht University, Utrecht, The Netherlands
| | - N M Korthagen
- Department of Orthopaedics, University Medical Center (UMC) Utrecht, Utrecht University, Utrecht, The Netherlands; Department of Equine Sciences, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands
| | - F P J G Lafeber
- Department of Rheumatology & Clinical Immunology, UMC Utrecht, Utrecht University, Utrecht, The Netherlands
| | - A M Zuurmond
- Metabolic Health Research, TNO, Leiden, the Netherlands
| | - I Bobeldijk
- Metabolic Health Research, TNO, Leiden, the Netherlands
| | - H Weinans
- Department of Orthopaedics, University Medical Center (UMC) Utrecht, Utrecht University, Utrecht, The Netherlands; Department of Rheumatology & Clinical Immunology, UMC Utrecht, Utrecht University, Utrecht, The Netherlands; Department of Biomechanical Engineering, Delft University of Technology, Delft, The Netherlands
| | - R Stoop
- Metabolic Health Research, TNO, Leiden, the Netherlands.
| |
Collapse
|
|
30
|
Kendzerska T, King LK, Lipscombe L, Croxford R, Stanaitis I, Hawker GA. The impact of hip and knee osteoarthritis on the subsequent risk of incident diabetes: a population-based cohort study. Diabetologia 2018; 61:2290-2299. [PMID: 30091045 DOI: 10.1007/s00125-018-4703-2] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/21/2018] [Accepted: 06/28/2018] [Indexed: 12/31/2022]
Abstract
AIMS/HYPOTHESIS This study examined the relationship between hip/knee osteoarthritis and incident diabetes. We hypothesised that hip/knee osteoarthritis would be independently related to an increased risk of incident diabetes and that this relationship would be due, at least in part, to walking difficulty. We also hypothesised a stronger relationship with incident diabetes for knee than hip osteoarthritis because of the higher prevalence in the former of obesity/the metabolic syndrome. METHODS A population cohort aged ≥55 years recruited from 1996 to 1998 was followed through provincial health administrative data to 2014. Participants with baseline diabetes were excluded. Hip/knee osteoarthritis was defined as swelling, pain or stiffness in any joint lasting 6 weeks in the past 3 months and indication on a joint homunculus that a hip/knee was 'troublesome'. Walking limitation was defined as self-reported difficulty standing or walking in the last 3 months (yes/no). Using Cox regressions, we examined the relationship of baseline hip/knee osteoarthritis with incident diabetes as defined from health administrative data, controlling for age, sex, BMI, income, prior hypertension, cardiovascular disease and primary care exposure. We tested whether the observed effect was mediated through walking limitation. RESULTS In total, 16,362 participants were included: median age 68 years and 61% female. Of these, 1637 (10%) individuals met the criteria for hip osteoarthritis, 2431 (15%) for knee osteoarthritis and 3908 (24%) for walking limitation. Over a median follow-up of 13.5 years (interquartile range 7.3-17.8), 3539 individuals (22%) developed diabetes. Controlling for confounders, a significant relationship was observed between number of hip/knee joints with osteoarthritis and incident diabetes: HR for two vs no osteoarthritic hips 1.25 (95% CI 1.08, 1.44); HR for two vs no osteoarthritic knees 1.16 (95% CI 1.04, 1.29). From 37% to 46% of this relationship was explained by baseline walking limitation. CONCLUSIONS/INTERPRETATION In a large population cohort aged ≥55 years who were free of diabetes at baseline, and controlling for confounders, the presence and burden of hip/knee osteoarthritis was a significant independent predictor of incident diabetes. This association was partially explained by walking limitation. Increased attention to osteoarthritis and osteoarthritis-related functional limitations has the potential to reduce diabetes risk.
Collapse
Affiliation(s)
- Tetyana Kendzerska
- Division of Respirology, Ottawa Hospital Research Institute, University of Ottawa, Ottawa Hospital, Civic Campus, 1053 Carling Ave, Ottawa, ON, K1Y 4E9, Canada.
- Institute for Clinical Evaluative Sciences, Ottawa, ON, Canada.
| | - Lauren K King
- Department of Medicine, University of Toronto, Toronto, ON, Canada
| | - Lorraine Lipscombe
- Department of Medicine, University of Toronto, Toronto, ON, Canada
- Women's College Research Institute, Women's College Hospital, Toronto, ON, Canada
- Institute for Clinical Evaluative Sciences, Toronto, ON, Canada
| | - Ruth Croxford
- Institute for Clinical Evaluative Sciences, Toronto, ON, Canada
| | - Ian Stanaitis
- Women's College Research Institute, Women's College Hospital, Toronto, ON, Canada
| | - Gillian A Hawker
- Department of Medicine, University of Toronto, Toronto, ON, Canada
- Women's College Research Institute, Women's College Hospital, Toronto, ON, Canada
- Institute for Clinical Evaluative Sciences, Toronto, ON, Canada
| |
Collapse
|
|
31
|
Lovecchio F, Fu MC, Iyer S, Steinhaus M, Albert T. Does Obesity Explain the Effect of the Metabolic Syndrome on Complications Following Elective Lumbar Fusion? A Propensity Score Matched Analysis. Global Spine J 2018; 8:683-689. [PMID: 30443477 PMCID: PMC6232719 DOI: 10.1177/2192568218765149] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
STUDY DESIGN Propensity score matched retrospective cohort study. OBJECTIVES Obesity is a major confounder in determining the independent effect of metabolic syndrome (MetS) on complications after spinal surgery. The purpose of this study is to differentiate MetS from obesity as an independent influence on perioperative outcomes after elective lumbar spine fusion. METHODS One- to 3-level posterior spinal fusion cases were identified from the 2011-2014 American College of Surgeons' National Surgical Quality Improvement Program. To determine the effects of MetS outside of obesity itself, patients with MetS were first compared to a no-MetS cohort and then to an obese-only no-MetS cohort. Two propensity score matches based on demographics, comorbidities, surgical complexity, and diagnosis were used to match patients in 1:1 ratios and compare outcomes. Logistic regression with propensity score adjustment was further utilized as a secondary method of reducing selection bias. RESULTS Out of 18 605 patients that met criteria for inclusion, 1903 (10.2%) met our definition of MetS. Patients with MetS had a higher rate of wound complications (3.8% vs 2.7% obese no MetS, P = .045; vs 2.6% no MetS, P = .035), readmissions (7.4% vs 2.2% obese no MetS, P < .001; vs 4.6% no MetS, P < .001), and extended length of stay (29.1% vs 23.9% obese no MetS, P < .001; vs 23.5% no MetS, P < .001). Patients with MetS were more likely to experience a wound complication (odds ratio = 1.47, 95% confidence interval = 1.02-2.12) or readmission (odds ratio = 1.48, 95% confidence interval = 1.22-1.80). CONCLUSIONS Even after controlling for obesity, MetS is an independent risk factor for adverse short-term outcomes. These findings have various implications for preoperative risk stratification and reduction strategies.
Collapse
Affiliation(s)
| | | | | | | | - Todd Albert
- Hospital for Special Surgery, New York, NY, USA
| |
Collapse
|
|
32
|
Collins KH, Sharif B, Reimer RA, Sanmartin C, Herzog W, Chin R, Marshall DA. Association of Metabolic Markers with self-reported osteoarthritis among middle-aged BMI-defined non-obese individuals: a cross-sectional study. BMC OBESITY 2018; 5:23. [PMID: 30186613 PMCID: PMC6120068 DOI: 10.1186/s40608-018-0201-9] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/27/2017] [Accepted: 05/24/2018] [Indexed: 12/31/2022]
Abstract
BACKGROUND Osteoarthritis (OA) is a chronic degenerative joint disease. While it is well-established that obesity affects OA through increased axial loading on the joint cartilage, the indirect effect of obesity through metabolic processes among the body mass index (BMI)-defined non-obese population, i.e., BMI < 30 kg/m2, is less known. Our goal was to evaluate the association of metabolic markers including body fat percentage (BF%), waist circumference, maximum weight gain during adulthood and serum creatinine with self-reported OA to establish if such measures offer additional information over BMI among the non-obese population between 40 and 65 years of age. METHODS Cross-sectional data from two cycles of the Canadian Health Measures Survey (CHMS) in 2007-2009 and 2009-2011 were analyzed. Sex-specific logistic regression models were developed to evaluate the association of self-reported OA with metabolic markers. Models were separately adjusted for age, BMI categories and serum creatinine, and a stratified analysis across BM categories was performed. In a secondary analysis, we evaluated the association of self-reported OA, cardiovascular diseases and hypertension across BF% categories. RESULTS Of 2462 individuals, 217 (8.8%) self-reported OA. After adjusting for age and BMI, those within BF%-defined overweight/obese category had 2.67 (95% CI: 1.32-3.51) and 2.11(95% CI: 1.38-3.21) times higher odds of reporting self-reported OA compared to those within BF%-defined athletic/acceptable category for females and males, respectively. BF% was also significantly associated with self-reported OA after adjusting for age and serum creatinine only among females (OR: 1.47, 95%CI: 1.12-1.84). Furthermore, among the BMI-defined overweight group, the age-adjusted odds of self-reported OA was significantly higher for overweight/obese BF% compared to athletic/acceptable BF% in both females and males. In a secondary analysis, we showed that the association of self-reported OA and hypertension/cardiovascular diseases is significantly higher among BF% overweight/obese (OR: 1.37, 95%CI: 1.19-3.09) compared to BF% athletic/acceptable (OR: 1.13, 95%CI: 0.87-2.82). CONCLUSION Our results provide corroborating evidence for a relationship between body fat and OA in a population-based study, while no significant independent correlates were found between other metabolic markers and OA prevalence. Future investigation on the longitudinal relationship between BF and OA among this sub-population may inform targeted prevention opportunities.
Collapse
Affiliation(s)
- Kelsey H. Collins
- Human Performance Laboratory, University of Calgary, Calgary, AB Canada
| | - Behnam Sharif
- Department of Community Health Sciences, University of Calgary, 3280 Hospital Drive NW, Calgary, AB T2N 4Z6 Canada
| | - Raylene A. Reimer
- Faculty of Kinesiology and Department of Biochemistry and Molecular Biology, University of Calgary, Calgary, AB Canada
| | | | - Walter Herzog
- Human Performance Laboratory, University of Calgary, Calgary, AB Canada
| | - Rick Chin
- Department of Medicine, University of Calgary, Calgary, AB Canada
| | - Deborah A. Marshall
- Department of Community Health Sciences, University of Calgary, 3280 Hospital Drive NW, Calgary, AB T2N 4Z6 Canada
| |
Collapse
|
|
33
|
Chen DS, Cao JG, Zhu B, Wang ZL, Wang TF, Tang JJ. Baicalin Attenuates Joint Pain and Muscle Dysfunction by Inhibiting Muscular Oxidative Stress in an Experimental Osteoarthritis Rat Model. Arch Immunol Ther Exp (Warsz) 2018; 66:453-461. [PMID: 30076457 DOI: 10.1007/s00005-018-0518-6] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/22/2017] [Accepted: 06/04/2018] [Indexed: 12/20/2022]
Abstract
Osteoarthritis (OA) is the most common degenerative joint disease, and causes major pain and disability in adults. It has been reported that muscle weakness and inflammation contribute to osteoarthritis development and progression. Oxidative stress plays important roles in muscle dysfunction and inflammation in osteomyelitis. Baicalin, the major active constituent of the isolated root of Scutellarialateriflora Georgi, has been shown to have anti-oxidative and anti-inflammatory effects. In this study, we evaluated the potential effects of baicalin on osteoarthritis. We established experimental osteoarthritis rat model, applied baicalin to the rats, and then explored the potential protective effect of baicalin on osteoarthritis severity, muscle dysfunction, and oxidative stress. Baicalin alleviated severity of OA in rats. Baicalin application attenuated muscle dysfunction in OA rats by increasing citrate synthase activity, myosin heavy chain IIa expression, and decreasing interleukin 6 production. Baicalin decreased muscular reactive oxygen species generation in OA rats. Baicalin inhibited nuclear factor erythroid-derived 2-like 2 expression in OA rats. Baicalin attenuated osteoarthritis in rat by inhibiting oxidative stress.
Collapse
Affiliation(s)
- De-Sheng Chen
- Department of Sports Injury and Arthroscopy, Tianjin Hospital, Tianjin, 300222, People's Republic of China.
| | - Jian-Gang Cao
- Department of Sports Injury and Arthroscopy, Tianjin Hospital, Tianjin, 300222, People's Republic of China
| | - Bo Zhu
- Department of Sports Injury and Arthroscopy, Tianjin Hospital, Tianjin, 300222, People's Republic of China
| | - Zeng-Liang Wang
- Department of Sports Injury and Arthroscopy, Tianjin Hospital, Tianjin, 300222, People's Republic of China
| | - Tong-Fu Wang
- Department of Sports Injury and Arthroscopy, Tianjin Hospital, Tianjin, 300222, People's Republic of China
| | - Jian-Jun Tang
- Department of Sports Injury and Arthroscopy, Tianjin Hospital, Tianjin, 300222, People's Republic of China
| |
Collapse
|
|
34
|
Adeyemi WJ, Olayaki LA. Diabetes escalates knee osteoarthritis in rats: Evidence of adaptive mechanism. ENVIRONMENTAL TOXICOLOGY AND PHARMACOLOGY 2018; 61:1-7. [PMID: 29803977 DOI: 10.1016/j.etap.2018.05.009] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/16/2018] [Revised: 05/17/2018] [Accepted: 05/19/2018] [Indexed: 06/08/2023]
Abstract
Clinical reports on the coexistence of diabetes mellitus (DM) and osteoarthritis (OA) dated back to the 1960 s. Therefore, the study investigated the effects of induced DM and/or knee osteoarthritis (KOA) on known biomarkers in male Wistar rats. Twenty rats of five animals per group were induced with DM and/or knee OA using streptozotocin plus nicotinamide and sodium monoiodoacetate. Afterwards, they were left untreated for four weeks.The results showed that pro-inflammatory and pro-oxidative events were most significantly expressed in D + OA group and least in OA group. In contrast to the other experimental groups, there was a decreased bone formation in DM group.Unexpectedly, there were significant increases in bone and cartilage degradation markers in diabetic group, relative to D + OA group. In conclusion, diabetic-osteoarthritic state is characterised by more altered biochemical profile, relative to what is probable in either disease condition. Nevertheless, this situation remains subject to the influence of endogenous homeostatic mechanisms.
Collapse
Affiliation(s)
- Wale Johnson Adeyemi
- Department of Physiology, College of Health Sciences, University of Ilorin, Ilorin, Kwara State, Nigeria.
| | - Luqman Aribidesi Olayaki
- Department of Physiology, College of Health Sciences, University of Ilorin, Ilorin, Kwara State, Nigeria.
| |
Collapse
|
|
35
|
Bihlet AR, Byrjalsen I, Bay-Jensen AC, Andersen JR, Christiansen C, Riis BJ, Valter I, Karsdal MA, Hochberg MC. Identification of pain categories associated with change in pain in patients receiving placebo: data from two phase 3 randomized clinical trials in symptomatic knee osteoarthritis. BMC Musculoskelet Disord 2018; 19:17. [PMID: 29343266 PMCID: PMC5773024 DOI: 10.1186/s12891-018-1938-5] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/23/2017] [Accepted: 01/11/2018] [Indexed: 01/04/2023] Open
Abstract
Background Pain is the principal clinical symptom of osteoarthritis (OA), and development of safe and effective analgesics for OA pain is needed. Drug development of new analgesics for OA pain is impaired by substantial change in pain in patients receiving placebo, and more data describing clinical characteristics and pain categories particularly associated with this phenomenon is needed. The purpose of this post-hoc analysis was to investigate clinical characteristics and pain categories and their association with radiographic progression and placebo pain reduction (PPR) in OA patients as measured the Western Ontario and McMasters Arthritis (WOMAC). Methods Pooled data from the placebo groups of two phase III randomized clinical trials in patients with knee OA followed for 2 years were analyzed. Differences between individual sub-scores and pain categories of weight-bearing and non-weight bearing pain over time were assessed. Selected patient baseline characteristics were assessed for association with PPR. Association between pain categories and radiographic progression was analyzed. Results The reduction of pain in placebo-treated patients was significantly higher in the composite of questions related to weight-bearing pain compared to non-weight-bearing pain of the target knee. Baseline BMI, age and JSW were not associated with pain change. Pain reduction was higher in the Target knee, compared to the Non-Target knee at all corresponding time-points. A very weak correlation was found between weight-bearing pain and progression in the non-target knee. Conclusions These results indicate that the reduction in pain in patients treated with placebo is significantly different between pain categories, as weight-bearing pain was significantly more reduced compared to non-weight-bearing pain. Further research in pain categories in OA is warranted. Trial Registration NCT00486434 (trial 1) and NCT00704847 (trial 2)
Collapse
Affiliation(s)
| | | | | | | | | | - Bente Juel Riis
- Nordic Bioscience, Herlev Hovedgade 207, DK2730, Herlev, Denmark
| | | | - Morten A Karsdal
- Nordic Bioscience, Herlev Hovedgade 207, DK2730, Herlev, Denmark
| | | |
Collapse
|
|
36
|
Abstract
Osteoarthritis (OA) is the most prevalent joint disease characterized by pain and degenerative lesions of the cartilage, subchondral bone, and other joint tissues. The causes of OA remain incompletely understood. Over the years, it has become recognized that OA is a multifactorial disease. In particular, aging and trauma are the main risk factors identified for the development of OA; however, other factors such as genetic predisposition, obesity, inflammation, gender and hormones, or metabolic syndrome contribute to OA development and lead to a more severe outcome. While this disease mainly affects people older than 60 years, OA developed after joint trauma affects all range ages and has a particular impact on young individuals and people who have highest levels of physical activity such as athletes. Traumatic injury to the joint often results in joint instability or intra-articular fractures which lead to posttraumatic osteoarthritis (PTOA). In response to injury, several molecular mechanisms are activated, increasing the production and activation of different factors that contribute to the progression of OA.In this chapter, we have focused on the interactions and contribution of the multiple factors involved in joint destruction and progression of OA. In addition, we overview the main changes and molecular mechanisms related to OA pathogenesis.
Collapse
|
|
37
|
Rishi L, Bhandari M, Kumar R. Can bariatric surgery delay the need for knee replacement in morbidly obese osteoarthritis patients. J Minim Access Surg 2018; 14:13-17. [PMID: 28695875 PMCID: PMC5749191 DOI: 10.4103/jmas.jmas_129_16] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
Objective: The objective of the study was to find the weight reduction pattern and its outcome on knee pain and function in osteoarthritis (OA) morbidly obese patients’ post-bariatric surgery with dietary and exercise changes. Methodology: Thirty morbidly obese (body mass index [BMI] >40 kg/m2) OA patients gave consent for bariatric surgery. Despite wearisome lifestyle modifications for weight loss and knee pain, satisfactory results were not retrieved. We took consent from all the patients predetermined for knee replacement in future because of pain and disability as recommended by knee replacement surgeon. The dietary and exercise protocol was standardised for all patients for bariatrics. Data for weight loss, change in BMI and Western Ontario and McMaster Universities Arthritis Index score consisting of pain, stiffness and activities of daily livings (ADLs) scores were documented at baseline, 3 months and 6 months post-bariatric surgery. Results The male-to-female ratio was 1:2. Mean age of the patients was 49.8 ± 8.6 years. Significant changes in pain (P < 0.001), stiffness (P < 0.001) and ADLs (P < 0.001) were found postoperatively at 3 and 6 months. Positive correlation of percentage change of BMI was seen with percentage change in pain (r = 0.479, P = 0.007) and ADLs (r = 0.414, P = 0.023) after 6 months of bariatric surgery. Most of the patients were inclined to delay the knee replacement further by the end of 6 months post-bariatric surgery. Conclusion: Bariatric surgery when combined with dietary and exercise changes gave significant results in terms of weight loss, knee pain and function. It is an approach that tackles both obesity and OA. It is a major step forward in stemming the global epidemic of these two interlinked conditions.
Collapse
Affiliation(s)
- Lajja Rishi
- Department of Physiotherapy, Sri Aurobindo Medical College and PG Institute, Mohak Bariatrics and Robitics, Indore, Madhya Pradesh, India
| | - Mohit Bhandari
- Department of Physiotherapy, Sri Aurobindo Medical College and PG Institute, Mohak Bariatrics and Robitics, Indore, Madhya Pradesh, India
| | - Ravindra Kumar
- Central Research Laboratory, Sri Aurobindo Medical College and PG Institute, Indore, Madhya Pradesh, India
| |
Collapse
|
|
38
|
Xie DX, Wei J, Zeng C, Yang T, Li H, Wang YL, Long HZ, Wu ZY, Qian YX, Li KH, Lei GH. Association between metabolic syndrome and knee osteoarthritis: a cross-sectional study. BMC Musculoskelet Disord 2017; 18:533. [PMID: 29246142 PMCID: PMC5732466 DOI: 10.1186/s12891-017-1890-9] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/18/2017] [Accepted: 12/01/2017] [Indexed: 12/17/2022] Open
Abstract
Background Osteoarthritis (OA) is the most prevalent chronic joint disease in China. The aim of this study was to examine the association between metabolic syndrome (MetS) and knee OA in a population-based Chinese study. Methods Data included in this analysis is from a cross-sectional study, i.e., the Xiangya Hospital Health Management Center Study. MetS was diagnosed according to the criteria defined by the Chinese Diabetes Society. Radiographic knee OA was defined as changes equivalent to Kellgren-Lawrence (K-L) grade 2 or above at least one side. Associations between MetS and its components with OA were evaluated by conducting multivariable adjusted logistic regression. Results A total of 5764 participants were included in the present study. The unadjusted OR (1.27, 95%CI: 1.10–1.47, P = 0.001), age-sex adjusted OR (1.17, 95%CI: 1.01–1.36, P = 0.041) and multivariable adjusted OR (1.17, 95%CI: 1.01–1.36, P = 0.043) all suggested a positive association between MetS and knee OA. Besides, its components (e.g., overweight, hypertension and dyslipidemia) were also associated with the prevalence of radiographic knee OA respectively, after adjusting for some confounding factors. In addition, with the accumulation of MetS components, the prevalence of knee OA increased. Furthermore, MetS as a whole was associated with the prevalence of knee osteophyte (OSP) (OR = 1.72, 95%CI: 1.42–2.09, P < 0.001), but not joint space narrowing (JSN) (OR = 1.06, 95%CI: 0.91–1.23, P = 0.449). Conclusions The findings of the present study indicated that there was a positive association between the prevalence of MetS and knee OA. However, MetS as a whole was associated with the higher prevalence of knee OSP, but not JSN, which should shed light on our understanding the association between MetS and OA.
Collapse
Affiliation(s)
- Dong-Xing Xie
- Department of Orthopaedics, Xiangya Hospital, Central South University, #87 Xiangya Road, Changsha, Hunan, 410008, People's Republic of China
| | - Jie Wei
- Health Management Center, Xiangya Hospital, Central South University, Changsha, Hunan Province, 410008, People's Republic of China.,Department of Epidemiology and Health Statistics, Xiangya School of Public Health, Central South University, Changsha, Hunan Province, 410008, People's Republic of China
| | - Chao Zeng
- Department of Orthopaedics, Xiangya Hospital, Central South University, #87 Xiangya Road, Changsha, Hunan, 410008, People's Republic of China
| | - Tuo Yang
- Department of Orthopaedics, Xiangya Hospital, Central South University, #87 Xiangya Road, Changsha, Hunan, 410008, People's Republic of China
| | - Hui Li
- Department of Orthopaedics, Xiangya Hospital, Central South University, #87 Xiangya Road, Changsha, Hunan, 410008, People's Republic of China
| | - Yi-Lun Wang
- Department of Orthopaedics, Xiangya Hospital, Central South University, #87 Xiangya Road, Changsha, Hunan, 410008, People's Republic of China
| | - Hui-Zhong Long
- Department of Orthopaedics, Xiangya Hospital, Central South University, #87 Xiangya Road, Changsha, Hunan, 410008, People's Republic of China
| | - Zi-Ying Wu
- Department of Orthopaedics, Xiangya Hospital, Central South University, #87 Xiangya Road, Changsha, Hunan, 410008, People's Republic of China
| | - Yu-Xuan Qian
- Department of Orthopaedics, Xiangya Hospital, Central South University, #87 Xiangya Road, Changsha, Hunan, 410008, People's Republic of China
| | - Kang-Hua Li
- Department of Orthopaedics, Xiangya Hospital, Central South University, #87 Xiangya Road, Changsha, Hunan, 410008, People's Republic of China
| | - Guang-Hua Lei
- Department of Orthopaedics, Xiangya Hospital, Central South University, #87 Xiangya Road, Changsha, Hunan, 410008, People's Republic of China.
| |
Collapse
|
|
39
|
Adeyemi WJ, Olayaki LA. Effects of single or combined induction of diabetes mellitus and knee osteoarthritis on some biochemical and haematological parameters in rats. Exp Mol Pathol 2017; 103:113-120. [PMID: 28757388 DOI: 10.1016/j.yexmp.2017.07.005] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/06/2017] [Revised: 07/18/2017] [Accepted: 07/26/2017] [Indexed: 12/16/2022]
Abstract
Clinical evidences on the coexistence of diabetes mellitus (DM) and osteoarthritis (OA) dated back to the 1960s. Therefore, the study investigated the effects of induced DM and/or knee osteoarthritis (KOA) on some biochemical and haematological parameters in adult male Wistar rats. Twenty rats were used for this study. They were randomly divided into 4 groups (N=5 rats) which included: Normal control; Osteoarthritic (OA) control; Diabetic control; and, Diabetic+Osteoarthritic (D+OA) control. DM was induced in overnight fasted rats by the administration of streptozotocin (65mg/kg b.w., i.p.) 15min after the administration of nicotinamide (110mg/kg, b.w., i.p.). However, KOA was induced by the intra-articular injection of 4mg of sodium monoiodoacetate in 40μl of normal saline. In the D+OA group, KOA was induced about 12h after the induction of DM. The rats were left untreated for four weeks. Afterwards, the experiment was terminated. The results showed that both DM and OA featured hypercortisolism and dyslipidaemia. The additive effects of both conditions were observed on the lipid profile and some haematological indices in the D+OA group. Unlike DM, OA had mild adverse effects on the haematological profile. Nevertheless, it significantly contributed to hyperglycaemia in the D+OA group, even though it had no significant effect on the insulin resistance. However, the hypocalcaemic and glycogenolytic effects of DM were negated by OA. In conclusion, the coexistence of DM and OA presents a greater challenge on the biochemical and haematological profiles than the individual disease. But, this prediction could sometimes be annulled by the intervention of endogenous homeostatic mechanisms.
Collapse
Affiliation(s)
- Wale J Adeyemi
- Department of Physiology, College of Health Sciences, University of Ilorin, Ilorin, Kwara State, Nigeria.
| | - Luqman A Olayaki
- Department of Physiology, College of Health Sciences, University of Ilorin, Ilorin, Kwara State, Nigeria
| |
Collapse
|
|
40
|
Frey N, Hügle T, Jick SS, Meier CR, Spoendlin J. Hyperlipidaemia and incident osteoarthritis of the hand: a population-based case-control study. Osteoarthritis Cartilage 2017; 25:1040-1045. [PMID: 28189828 DOI: 10.1016/j.joca.2017.01.014] [Citation(s) in RCA: 32] [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: 06/21/2016] [Revised: 01/03/2017] [Accepted: 01/25/2017] [Indexed: 02/02/2023]
Abstract
OBJECTIVE Preclinical evidence suggests that increased cholesterol levels might be involved in the pathophysiology of osteoarthritis of the hand (HOA), but evidence from observational studies remains scarce. We aimed to analyse the association between hyperlipidaemia and incident HOA. DESIGN We conducted a matched (1:1) case-control study using the UK-based Clinical Practice Research Datalink (CPRD). Cases were patients aged 30-89 years with an incident diagnosis of HOA between 1995 and 2014. In multivariable conditional logistic regression analyses, we calculated odds ratios (OR) for incident HOA in patients with hyperlipidaemia, categorized by gender, age, previous duration of hyperlipidaemia, and recent statin treatment. RESULTS Among 19,590 cases and 19,590 controls, we observed an increased risk of HOA in patients with hyperlipidaemia (OR 1.37, 95% confidence intervals (CI) 1.28-1.47), when compared to patients without hyperlipidaemia. Thus, of all HOA cases in our study population, 3.6% may have been attributable to the presence of hyperlipidaemia (population attributable risk). Most patients with HOA were elderly, but the strength of the association between HOA and hyperlipidaemia inversely correlated with increasing age, with the highest OR of 1.72 (95% CI 1.24-2.38) in patients aged 29-49 years. Categorization by previous hyperlipidaemia duration, as well as sub-classification of patients with hyperlipidaemia into those with and without recent statin use did not meaningfully change the effect estimate. CONCLUSIONS Our results suggest that hyperlipidaemia may be an independent risk factor for new onset HOA.
Collapse
Affiliation(s)
- N Frey
- Basel Pharmacoepidemiology Unit, Division of Clinical Pharmacy and Epidemiology, Department of Pharmaceutical Sciences, University of Basel, Basel, Switzerland; Hospital Pharmacy, University Hospital Basel, Basel, Switzerland
| | - T Hügle
- Orthopaedics Clinic, University Hospital Basel, Switzerland
| | - S S Jick
- Boston Collaborative Drug Surveillance Program, Boston University, Lexington, United States
| | - C R Meier
- Basel Pharmacoepidemiology Unit, Division of Clinical Pharmacy and Epidemiology, Department of Pharmaceutical Sciences, University of Basel, Basel, Switzerland; Hospital Pharmacy, University Hospital Basel, Basel, Switzerland; Boston Collaborative Drug Surveillance Program, Boston University, Lexington, United States.
| | - J Spoendlin
- Basel Pharmacoepidemiology Unit, Division of Clinical Pharmacy and Epidemiology, Department of Pharmaceutical Sciences, University of Basel, Basel, Switzerland; Hospital Pharmacy, University Hospital Basel, Basel, Switzerland
| |
Collapse
|
|
41
|
Does metformin protect against osteoarthritis? An electronic health record cohort study. Prim Health Care Res Dev 2017; 18:623-628. [PMID: 28539134 DOI: 10.1017/s1463423617000287] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022] Open
Abstract
BACKGROUND Obesity is a major risk factor for osteoarthritis (OA) whilst there is some evidence that diabetes also increases risk. Metformin is a common oral treatment for those with diabetes. OBJECTIVE The aim is to investigate whether metformin reduces the risk of OA. METHODS This was a cohort study set within the Consultations in Primary Care Archive, with 3217 patients with type 2 diabetes. Patients at 13 general practices with recorded type 2 diabetes in the baseline period (2002-2003) and no prior record of OA were identified. Exposure was a prescription for metformin. Outcome was an OA record during follow up. Cox proportional hazard models with Gamma frailty term were fitted: adjusted for age, gender, deprivation, and comorbidity. RESULTS There was no association between prescribed metformin treatment at baseline and OA (adjusted HR: 1.02, 95% CI: 0.91, 1.15). A similar non- significant association was found when allowing exposure status of prescription of metformin to vary over time.
Collapse
|
|
42
|
Appleton CT, Hawker GA, Hill CL, Pope JE. Editorial: “Weighing in” on the Framingham Osteoarthritis Study: Measuring Biomechanical and Metabolic Contributions to Osteoarthritis. Arthritis Rheumatol 2017; 69:1127-1130. [DOI: 10.1002/art.40089] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2017] [Accepted: 03/02/2017] [Indexed: 11/10/2022]
Affiliation(s)
| | - Gillian A. Hawker
- University of Toronto, Women's College Research Institute, Women's College Hospital, and Institute for Clinical Evaluative SciencesToronto Ontario Canada
| | - Catherine L. Hill
- The Queen Elizabeth Hospital, Woodville, South Australia, Australia, and the Health Observatory, University of AdelaideAdelaide South Australia Australia
| | - Janet E. Pope
- Western University and St. Joseph's Health CareLondon Ontario Canada
| |
Collapse
|
|
43
|
Papachristou NI, Blair HC, Kypreos KE, Papachristou DJ. High-density lipoprotein (HDL) metabolism and bone mass. J Endocrinol 2017; 233:R95-R107. [PMID: 28314771 PMCID: PMC5598779 DOI: 10.1530/joe-16-0657] [Citation(s) in RCA: 52] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/16/2017] [Accepted: 03/17/2017] [Indexed: 02/06/2023]
Abstract
It is well appreciated that high-density lipoprotein (HDL) and bone physiology and pathology are tightly linked. Studies, primarily in mouse models, have shown that dysfunctional and/or disturbed HDL can affect bone mass through many different ways. Specifically, reduced HDL levels have been associated with the development of an inflammatory microenvironment that affects the differentiation and function of osteoblasts. In addition, perturbation in metabolic pathways of HDL favors adipoblastic differentiation and restrains osteoblastic differentiation through, among others, the modification of specific bone-related chemokines and signaling cascades. Increased bone marrow adiposity also deteriorates bone osteoblastic function and thus bone synthesis, leading to reduced bone mass. In this review, we present the current knowledge and the future directions with regard to the HDL-bone mass connection. Unraveling the molecular phenomena that underline this connection will promote the deeper understanding of the pathophysiology of bone-related pathologies, such as osteoporosis or bone metastasis, and pave the way toward the development of novel and more effective therapies against these conditions.
Collapse
Affiliation(s)
- Nicholaos I Papachristou
- Department of Anatomy-Histology-EmbryologyUnit of Bone and Soft Tissue Studies, University of Patras Medical School, Patras, Greece
| | - Harry C Blair
- Department of PathologyUniversity of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA
- Pittsburgh VA Medical CenterPittsburgh, Pennsylvania, USA
| | - Kyriakos E Kypreos
- Department of PharmacologyUniversity of Patras Medical School, Patras, Greece
| | - Dionysios J Papachristou
- Department of Anatomy-Histology-EmbryologyUnit of Bone and Soft Tissue Studies, University of Patras Medical School, Patras, Greece
- Department of PathologyUniversity of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA
| |
Collapse
|
|
44
|
Hsu CC, Lin CL, Jou IM, Wang PH, Lee JS. The protective role of nitric oxide-dependent innate immunosuppression in the early stage of cartilage damage in rats: Role of nitric oxide in cartilage damage. Bone Joint Res 2017; 6:253-258. [PMID: 28450318 PMCID: PMC5426177 DOI: 10.1302/2046-3758.64.bjj-2016-0161.r1] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/13/2022] Open
Abstract
Objectives Osteoarthritis (OA) is the most common form of arthritis, affecting approximately 15% of the human population. Recently, increased concentration of nitric oxide in serum and synovial fluid in patients with OA has been observed. However, the exact role of nitric oxide in the initiation of OA has not been elucidated. The aim of the present study was to investigate the role of nitric oxide in innate immune regulation during OA initiation in rats. Methods Rat OA was induced by performing meniscectomy surgery while cartilage samples were collected 0, 7, and 14 days after surgery. Cartilage cytokine levels were determined by using enzyme-linked immunosorbent assay, while other proteins were assessed by using Western blot Results In the time course of the study, nitric oxide was increased seven and 14 days after OA induction. Pro-inflammatory cytokines including tumour necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6 were decreased. L-NG-Nitroarginine methyl ester (L-NAME, a non-specific nitric oxide synthase inhibitor) significantly decreased cartilage nitric oxide and blocked immune suppression. Further, L-NAME decreased Matrix metalloproteinase (MMPs) and increased tissue inhibitor of metalloproteinase (TIMP) expression in meniscectomised rats. Conclusion Nitric oxide-dependent innate immune suppression protects cartilage from damage in the early stages of OA initiation in rats. Cite this article: C-C. Hsu, C-L. Lin, I-M. Jou, P-H. Wang, J-S. Lee. The protective role of nitric oxide-dependent innate immunosuppression in the early stage of cartilage damage in rats: Role of nitric oxide in ca rtilage da mage. Bone Joint Res 2017;6:253–258. DOI: 10.1302/2046-3758.64.BJJ-2016-0161.R1.
Collapse
Affiliation(s)
- C-C Hsu
- Department of Orthopedics, College of Medicine, Tainan, Taiwan
| | - C-L Lin
- College of Medicine, National Cheng Kung University Hospital, Tainan, Taiwan
| | - I-M Jou
- Department of Orthopedics, National Cheng Kung University Hospital, No.138 Sheng-Li Road, 704 Tainan, and Orthopedics Department, E-Da Hospital, No. 1 Yida Road, Jiao-su Village, Yan-Chao District, Kaohsiung City, Taiwan
| | - P-H Wang
- Department of Orthopedics, Chi-Mei Medical Center, No.901, Zhonghua Rd, 710 Tainan, Taiwan
| | - J-S Lee
- Department of Neurosurgery, National Cheng Kung University Hospital, No.138 Sheng-Li Road, 704 Tainan, Taiwan
| |
Collapse
|
|
45
|
Gregson CL, Hardcastle SA, Murphy A, Faber B, Fraser WD, Williams M, Davey Smith G, Tobias JH. High Bone Mass is associated with bone-forming features of osteoarthritis in non-weight bearing joints independent of body mass index. Bone 2017; 97:306-313. [PMID: 28082078 PMCID: PMC5378151 DOI: 10.1016/j.bone.2017.01.005] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/16/2016] [Revised: 11/05/2016] [Accepted: 01/06/2017] [Indexed: 12/19/2022]
Abstract
OBJECTIVES High Bone Mass (HBM) is associated with (a) radiographic knee osteoarthritis (OA), partly mediated by increased BMI, and (b) pelvic enthesophytes and hip osteophytes, suggestive of a bone-forming phenotype. We aimed to establish whether HBM is associated with radiographic features of OA in non-weight-bearing (hand) joints, and whether such OA demonstrates a bone-forming phenotype. METHODS HBM cases (BMD Z-scores≥+3.2) were compared with family controls. A blinded assessor graded all PA hand radiographs for: osteophytes (0-3), joint space narrowing (JSN) (0-3), subchondral sclerosis (0-1), at the index Distal Interphalangeal Joint (DIPJ) and 1st Carpometacarpal Joint (CMCJ), using an established atlas. Analyses used a random effects logistic regression model, adjusting a priori for age and gender. Mediating roles of BMI and bone turnover markers (BTMs) were explored by further adjustment. RESULTS 314 HBM cases (mean age 61.1years, 74% female) and 183 controls (54.3years, 46% female) were included. Osteophytes (grade≥1) were more common in HBM (DIPJ: 67% vs. 45%, CMCJ: 69% vs. 50%), with adjusted OR [95% CI] 1.82 [1.11, 2.97], p=0.017 and 1.89 [1.19, 3.01], p=0.007 respectively; no differences were seen in JSN. Further adjustment for BMI failed to attenuate ORs for osteophytes in HBM cases vs. controls; DIPJ 1.72 [1.05, 2.83], p=0.032, CMCJ 1.76 [1.00, 3.06], p=0.049. Adjustment for BTMs (concentrations lower amongst HBM cases) did not attenuate ORs. CONCLUSIONS HBM is positively associated with OA in non-weight-bearing joints, independent of BMI. HBM-associated OA is characterised by osteophytes, consistent with a bone-forming phenotype, rather than JSN reflecting cartilage loss. Systemic factors (e.g. genetic architecture) which govern HBM may also increase bone-forming OA risk.
Collapse
Affiliation(s)
- C L Gregson
- Musculoskeletal Research Unit, School of Clinical Sciences, University of Bristol, UK.
| | - S A Hardcastle
- Musculoskeletal Research Unit, School of Clinical Sciences, University of Bristol, UK; MRC Integrative Epidemiology Unit, University of Bristol, Bristol, UK
| | - A Murphy
- Musculoskeletal Research Unit, School of Clinical Sciences, University of Bristol, UK
| | - B Faber
- Musculoskeletal Research Unit, School of Clinical Sciences, University of Bristol, UK
| | - W D Fraser
- Department of Medicine, Norwich Medical School, University of East Anglia, Norwich, UK
| | - M Williams
- Department of Radiology, North Bristol NHS Trust, Bristol, UK
| | - G Davey Smith
- MRC Integrative Epidemiology Unit, University of Bristol, Bristol, UK
| | - J H Tobias
- Musculoskeletal Research Unit, School of Clinical Sciences, University of Bristol, UK
| |
Collapse
|
|
46
|
Xu X, Liu L, Xie W, Zhang Y, Zeng H, Zhang F, Reis C, Cao X, Zhao Y. Increase in the prevalence of arthritis in adulthood among adults exposed to Chinese famine of 1959 to 1961 during childhood: A cross-sectional survey. Medicine (Baltimore) 2017; 96:e6496. [PMID: 28353598 PMCID: PMC5380282 DOI: 10.1097/md.0000000000006496] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/20/2023] Open
Abstract
The developmental origins hypothesis postulates that under-nutrition in the early stage of life is associated with an increased risk of disease in adulthood. This study aimed to examine the association of exposure to the Chinese famine of 1959 to 1961 in early life with the risk of arthritis in adulthood.From July to September 2009, the study adopted multistage stratified random sampling cross-sectional survey to recruit 1224 eligible adults in Chongqing. Famine exposure groups were categorized into 3 groups: (1) childhood exposure, (2) fetal exposure, and (3) nonexposure. Self-reported arthritis of physician diagnosis was obtained. A total of 1224 eligible respondents were interviewed, including 299 individuals exposed during childhood, 455 exposed when fetal, and 470 without exposure.The prevalence of arthritis in adulthood among individuals exposed to famine during childhood was significantly higher than those not exposed (17.39% vs 11.28%, odds ratio [OR] = 1.573 with a 95% confidence interval of [CI] [1.020, 2.424]). Persons exposed to famine during the fetal period did not significantly contribute to a higher rate of arthritis in adulthood than those who were not exposed to famine (13.19% vs 11.28%, OR = 1.072, 95% CI = 0.713, 1.613). In addition, education level, the average monthly income, sleep status, and satisfaction of the present living condition were associated with the risk of arthritis in adulthood.Exposure to the Chinese famine during childhood may be associated with an increased risk of arthritis in adulthood. This study suggests that early life nutrition may have an effect on the risk of arthritis in adulthood.
Collapse
Affiliation(s)
- Xianglong Xu
- School of Public Health and Management
- Research Center for Medicine and Social Development
- The Innovation Center for Social Risk Governance in Health
| | - Lingli Liu
- School of Public Health and Management
- Research Center for Medicine and Social Development
- The Innovation Center for Social Risk Governance in Health
| | - Wenxi Xie
- School of the Second Clinical, Chongqing Medical University, Chongqing, China
| | - Yong Zhang
- School of Public Health and Management
- Research Center for Medicine and Social Development
- The Innovation Center for Social Risk Governance in Health
| | - Huan Zeng
- School of Public Health and Management
- Research Center for Medicine and Social Development
- The Innovation Center for Social Risk Governance in Health
| | - Fan Zhang
- School of Public Health and Management
- Research Center for Medicine and Social Development
- The Innovation Center for Social Risk Governance in Health
| | - Cesar Reis
- Department of Preventive Medicine, Loma Linda University Medical Center, CA
| | - Xianqing Cao
- School of Public Health and Management
- Research Center for Medicine and Social Development
- The Innovation Center for Social Risk Governance in Health
| | - Yong Zhao
- School of Public Health and Management
- Research Center for Medicine and Social Development
- The Innovation Center for Social Risk Governance in Health
| |
Collapse
|
|
47
|
Sekar S, Crawford R, Xiao Y, Prasadam I. Dietary Fats and Osteoarthritis: Insights, Evidences, and New Horizons. J Cell Biochem 2016; 118:453-463. [DOI: 10.1002/jcb.25758] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/09/2016] [Accepted: 10/10/2016] [Indexed: 12/11/2022]
Affiliation(s)
- Sunderajhan Sekar
- Institute of Health and Biomedical Innovation; Queensland University of Technology; Brisbane Australia
| | - Ross Crawford
- Institute of Health and Biomedical Innovation; Queensland University of Technology; Brisbane Australia
- The Prince Charles Hospital; Orthopedic Department; Brisbane Australia
| | - Yin Xiao
- Institute of Health and Biomedical Innovation; Queensland University of Technology; Brisbane Australia
| | - Indira Prasadam
- Institute of Health and Biomedical Innovation; Queensland University of Technology; Brisbane Australia
| |
Collapse
|
|
48
|
Garessus EDG, de Mutsert R, Visser AW, Rosendaal FR, Kloppenburg M. No association between impaired glucose metabolism and osteoarthritis. Osteoarthritis Cartilage 2016; 24:1541-7. [PMID: 27084351 DOI: 10.1016/j.joca.2016.04.007] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/21/2015] [Revised: 03/21/2016] [Accepted: 04/04/2016] [Indexed: 02/02/2023]
Abstract
OBJECTIVE To investigate the association between markers of glucose metabolism and hand and knee osteoarthritis (OA). METHODS This is a cross-sectional analysis of baseline measurements of the Netherlands Epidemiology of Obesity (NEO) study, a population-based prospective cohort study. Fasting glucose, insulin and glycated hemoglobulin A1c (HbA1c) concentrations were measured, Homeostasis Model Assessment for Insulin Resistance (HOMA-IR) was calculated and clinical OA was defined following the American College of Rheumatology (ACR) criteria. After exclusion of participants on glucose-lowering drugs, odds ratios (ORs) with 95% confidence intervals (CIs) for either hand, knee or both hand and knee OA were calculated (no OA as reference), as a function of each marker of glucose metabolism, with logistic regression analyses. Models were adjusted for age, ethnicity, education, height, weight and total body fat, and stratified by sex. RESULTS In 6197 participants (age 45-65 years, 56% women, mean body mass index (BMI) 26 kg/m(2)), prevalences of hand OA, knee OA or both were 7%, 10% or 4%, respectively. In men, the adjusted OR (95%CI) for hand OA was 1.18 (1.01-1.39) per standard deviation (SD) increase in plasma glucose (0.85 mmol/L). There were no further associations of glucose, HbA1c, insulin and HOMA-IR with the different types of OA, neither in men nor in women. CONCLUSION An impaired glucose metabolism does not seem be related to OA. In men, an association was observed for fasting glucose concentrations and hand OA. Future studies should investigate the presence of sex differences in the pathogenesis of hand OA.
Collapse
Affiliation(s)
- E D G Garessus
- Department of Rheumatology, Leiden University Medical Center, C1-R, P.O. Box 9600, Leiden 2300 RC, The Netherlands.
| | - R de Mutsert
- Department of Clinical Epidemiology, Leiden University Medical Center, C7-P, P.O. Box 9600, Leiden 2300 RC, The Netherlands.
| | - A W Visser
- Department of Rheumatology, Leiden University Medical Center, C1-R, P.O. Box 9600, Leiden 2300 RC, The Netherlands.
| | - F R Rosendaal
- Department of Clinical Epidemiology, Leiden University Medical Center, C7-P, P.O. Box 9600, Leiden 2300 RC, The Netherlands; Department of Thrombosis and Hemostasis, Leiden University Medical Center, C7-P, P.O. Box 9600, Leiden 2300 RC, The Netherlands.
| | - M Kloppenburg
- Department of Rheumatology, Leiden University Medical Center, C1-R, P.O. Box 9600, Leiden 2300 RC, The Netherlands; Department of Clinical Epidemiology, Leiden University Medical Center, C7-P, P.O. Box 9600, Leiden 2300 RC, The Netherlands.
| |
Collapse
|
|
49
|
Li H, George DM, Jaarsma RL, Mao X. Metabolic syndrome and components exacerbate osteoarthritis symptoms of pain, depression and reduced knee function. ANNALS OF TRANSLATIONAL MEDICINE 2016; 4:133. [PMID: 27162783 DOI: 10.21037/atm.2016.03.48] [Citation(s) in RCA: 72] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/13/2023]
Abstract
BACKGROUND The purpose of this study was to investigate the prevalence of metabolic syndrome and its co-morbidities in patients with primary knee osteoarthritis and to assess if the severity of metabolic syndrome, and components, correlates with the severity of osteoarthritis symptoms. METHODS A case controlled analysis of 70 patients with osteoarthritis compared to a control group of 81 patients. Each patient underwent clinical review including history, examination, and pathology tests. The case-group all had stage IV osteoarthritis as determined by radiographs and intra-operative assessment. In addition a visual analogue scale (VAS), Hospital for Special Surgery knee score (HSS), and Hamilton Depression scores were completed. RESULTS The prevalence of hypertension, obesity, dyslipidemia and metabolic syndrome was significantly higher in the patients with osteoarthritis compared to the control group. There is a significant correlation between the degree of hypertension, the presence of dyslipidemia or hyperglycemia and the severity of osteoarthritis symptoms. Variables hypertension, low HDL-C levels, and the number of co-morbidities were all identified as risk factors for increased osteoarthritis symptoms. CONCLUSIONS There is a correlation between the number of metabolic disorders, the severity of hypertension and severity of osteoarthritis symptoms. Hypertension and decreased HDL-cholesterol were positive risk factors for increased osteoarthritis symptomatology.
Collapse
Affiliation(s)
- Hongxing Li
- 1 Department of Orthopaedic Surgery, Central Hospital of Shaoyang, Shaoyang 422000, China ; 2 Department of Orthopaedics, School of Medicine, Flinders University, Adelaide, Australia ; 3 Department of Orthopaedics and Trauma, Flinders Medical Centre, Adelaide, Australia ; 4 Department of Orthopaedic Surgery, 2nd Xiangya Hospital, Changsha 410011, China
| | - Daniel M George
- 1 Department of Orthopaedic Surgery, Central Hospital of Shaoyang, Shaoyang 422000, China ; 2 Department of Orthopaedics, School of Medicine, Flinders University, Adelaide, Australia ; 3 Department of Orthopaedics and Trauma, Flinders Medical Centre, Adelaide, Australia ; 4 Department of Orthopaedic Surgery, 2nd Xiangya Hospital, Changsha 410011, China
| | - Ruurd L Jaarsma
- 1 Department of Orthopaedic Surgery, Central Hospital of Shaoyang, Shaoyang 422000, China ; 2 Department of Orthopaedics, School of Medicine, Flinders University, Adelaide, Australia ; 3 Department of Orthopaedics and Trauma, Flinders Medical Centre, Adelaide, Australia ; 4 Department of Orthopaedic Surgery, 2nd Xiangya Hospital, Changsha 410011, China
| | - Xinzhan Mao
- 1 Department of Orthopaedic Surgery, Central Hospital of Shaoyang, Shaoyang 422000, China ; 2 Department of Orthopaedics, School of Medicine, Flinders University, Adelaide, Australia ; 3 Department of Orthopaedics and Trauma, Flinders Medical Centre, Adelaide, Australia ; 4 Department of Orthopaedic Surgery, 2nd Xiangya Hospital, Changsha 410011, China
| |
Collapse
|
|
50
|
de Munter W, van den Bosch MH, Slöetjes AW, Croce KJ, Vogl T, Roth J, Koenders MI, van de Loo FA, van den Berg WB, van der Kraan PM, van Lent PL. High LDL levels lead to increased synovial inflammation and accelerated ectopic bone formation during experimental osteoarthritis. Osteoarthritis Cartilage 2016; 24:844-55. [PMID: 26687826 DOI: 10.1016/j.joca.2015.11.016] [Citation(s) in RCA: 49] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/07/2015] [Revised: 11/03/2015] [Accepted: 11/24/2015] [Indexed: 02/02/2023]
Abstract
OBJECTIVE A relation between osteoarthritis (OA) and increased cholesterol levels is apparent. In the present study we investigate OA pathology in apolipoprotein E (ApoE)(-)(/-) mice with and without a cholesterol-rich diet, a model for high systemic low density lipoprotein (LDL) cholesterol levels independent of weight. METHOD Wild type (WT), Apoe(-)(/-), S100a9(-/-) and Apoe(-)(/-)S100a9(-/-) mice (C57BL/6 background) received a standard or cholesterol-rich diet. Experimental OA was induced by intra-articular injection of collagenase and animals were sacrificed at day 10 and day 36. RESULTS Although minimal differences in cartilage damage were found between the WT and ApoE(-)(/-) mice, increased synovial thickening was found in the latter. Thirty-six days after OA-induction, ApoE(-)(/-) mice on a standard diet showed increased ectopic bone formation, particularly at the medial collateral ligament, compared with OA in WT mice. Furthermore, a significant increase in synovial gene expression of both S100a8 and S100a9 and S100A8/S100A9 protein levels was found in ApoE(-)(/-) mice, suggesting an activated inflammatory status of synovial cells. In both ApoE(-)(/-) and WT mice, addition of a cholesterol-rich diet resulted in excessive bone formation in the medial collateral ligament at late-time-point OA. Interestingly, at the early time point, proteoglycan deposition was already significantly increased in ApoE(-)(/-) mice compared with WT mice. Mice deficient for both ApoE and S100a9 also showed increased ectopic bone formation, but not synovial activation, suggesting a role for S100-proteins in cholesterol-mediated synovial activation. CONCLUSIONS Increased cholesterol levels strongly elevate synovial activation and ectopic bone formation in early-stage collagenase-induced OA.
Collapse
Affiliation(s)
- W de Munter
- Experimental Rheumatology, Radboud university medical center, Nijmegen, The Netherlands.
| | - M H van den Bosch
- Experimental Rheumatology, Radboud university medical center, Nijmegen, The Netherlands.
| | - A W Slöetjes
- Experimental Rheumatology, Radboud university medical center, Nijmegen, The Netherlands.
| | - K J Croce
- Center for Interdisciplinary Cardiovascular Sciences, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
| | - T Vogl
- Institute of Immunology, University of Muenster, Muenster, Germany.
| | - J Roth
- Institute of Immunology, University of Muenster, Muenster, Germany.
| | - M I Koenders
- Experimental Rheumatology, Radboud university medical center, Nijmegen, The Netherlands.
| | - F A van de Loo
- Experimental Rheumatology, Radboud university medical center, Nijmegen, The Netherlands.
| | - W B van den Berg
- Experimental Rheumatology, Radboud university medical center, Nijmegen, The Netherlands.
| | - P M van der Kraan
- Experimental Rheumatology, Radboud university medical center, Nijmegen, The Netherlands.
| | - P L van Lent
- Experimental Rheumatology, Radboud university medical center, Nijmegen, The Netherlands.
| |
Collapse
|