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Al-Samerria S, Xu H, Diaz-Rubio ME, Phelan J, Su C, Ma K, Newen A, Li K, Yamada S, Negron AL, Wondisford F, Radovick S. Biomarkers of GH deficiency identified in untreated and GH-treated Pit-1 mutant mice. Front Endocrinol (Lausanne) 2025; 16:1539797. [PMID: 40370773 PMCID: PMC12074916 DOI: 10.3389/fendo.2025.1539797] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/04/2024] [Accepted: 03/13/2025] [Indexed: 05/16/2025] Open
Abstract
Background Growth Hormone Deficiency (GHD) is marked by insufficient growth hormone (GH) production, leading to disruptions in growth and metabolism. Its diagnosis is challenging due to the lack of sensitive, specific tests. To address this, we used a novel mouse model with a POU1F1 (Pit-1) gene mutation (K216E). This study aimed to identify metabolic biomarkers of GHD and assess their responsiveness to GH therapy, alongside pathway analysis to uncover disrupted metabolic pathways. Methods The Pit-1^K216E mouse model was validated for GHD through assessments of GH production, growth, and body composition. Metabolomic profiling was conducted to identify biomarkers, while pathway analysis examined disrupted metabolic pathways and their response to GH treatment. This approach aimed to improve understanding of GHD's metabolic impact and potential therapeutic strategies. Results The assessment of the Pit-1^K216E mouse confirmed GHD, as evidenced by reduced GH production and altered body composition. Metabolomic profiling identified three distinct biomarker groups associated with GHD: (1) GHD Biomarkers, found exclusively in GH-deficient mutant mice but absent in WT controls; (2) GH Treatment Responsive Biomarkers, which were altered in GH-deficient mutant mice (GHD) and further modulated following GH treatment, reflecting a response specific to the GHD condition and its treatment, but not observed in WT mice; and (3) GH Treatment-Specific Responsive Biomarkers, observed exclusively in the GHD condition after GH therapy. Pathway analysis revealed significant disruptions in purine metabolism, amino acid metabolism, and protein synthesis, with notable sex-specific differences. Male mice exhibited imbalances in taurine and hypotaurine metabolism, while female mice showed disruptions in tyrosine metabolism and mitochondrial function, highlighting sex-dependent metabolic responses to GHD and GH therapy. Conclusion The Pit-1^K216E mouse model offers a robust platform for exploring GHD's molecular mechanisms. The identification of distinct, sex-specific metabolic biomarkers provides insights into GHD-related metabolic disruptions and supports personalized management strategies. These findings establish a framework for leveraging metabolic biomarkers to enhance the diagnosis and monitoring of GHD, with promising applications for future human studies and therapeutic strategies.
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Affiliation(s)
- Sarmed Al-Samerria
- Department of Pediatrics, University of Arizona College of Medicine, Phoenix, AZ, United States
| | - Huiting Xu
- Department of Medicine, Robert Wood Johnson Medical School, Rutgers, The State University of New Jersey, New Brunswick, NJ, United States
| | - M. Elena Diaz-Rubio
- Rutgers Cancer Institute, Robert Wood Johnson Medical School, Rutgers, The State University of New Jersey, New Brunswick, NJ, United States
| | - Joseph Phelan
- Department of Medicine, Robert Wood Johnson Medical School, Rutgers, The State University of New Jersey, New Brunswick, NJ, United States
| | - Chi Su
- Department of Medicine, Robert Wood Johnson Medical School, Rutgers, The State University of New Jersey, New Brunswick, NJ, United States
| | - Keer Ma
- Department of Medicine, Robert Wood Johnson Medical School, Rutgers, The State University of New Jersey, New Brunswick, NJ, United States
| | - Anna Newen
- Department of Medicine, Robert Wood Johnson Medical School, Rutgers, The State University of New Jersey, New Brunswick, NJ, United States
| | - Kiana Li
- Department of Medicine, Robert Wood Johnson Medical School, Rutgers, The State University of New Jersey, New Brunswick, NJ, United States
| | - Sayaka Yamada
- Department of Medicine, University of Arizona College of Medicine, Phoenix, AZ, United States
| | - Ariel L. Negron
- Department of Pediatrics, University of Arizona College of Medicine, Phoenix, AZ, United States
| | - Fredric Wondisford
- Department of Medicine, University of Arizona College of Medicine, Phoenix, AZ, United States
| | - Sally Radovick
- Department of Pediatrics, University of Arizona College of Medicine, Phoenix, AZ, United States
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Kacprzak B, Stańczak M, Bielenda B, Yarmohammadi AA, Hagner-Derengowska M. Molecular Aspects of Cartilage Microfracturation: Rehabilitation Insights. Orthop Rev (Pavia) 2025; 17:129917. [PMID: 40276361 PMCID: PMC12021420 DOI: 10.52965/001c.129917] [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: 11/02/2024] [Accepted: 12/16/2024] [Indexed: 04/26/2025] Open
Abstract
Cartilage microfracturation is a surgical technique specifically designed to address chondral defects, which are injuries to the cartilage that covers the ends of bones in joints. These defects can result from traumatic injuries, degenerative conditions such as osteoarthritis, or congenital abnormalities. The primary objective of microfracture surgery is to promote the regeneration of functional cartilage tissue, thereby restoring joint function, alleviating pain, and enhancing mobility. The procedure involves creating small, controlled perforations, or microfractures, in the subchondral bone plate beneath the damaged cartilage. This process, performed with precision to minimize damage to surrounding healthy tissue, penetrates the subchondral bone to reach the bone marrow, which is rich in mesenchymal stem cells (MSCs).
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Affiliation(s)
| | - Mikołaj Stańczak
- AECC University College, Bournemouth, UK
- Volleybox, Gliwice, Poland
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Wang CC, Huang KC, Ku MC, Pan CC, Hsieh CP, Chang IL, Tzeng CY, Chen CP, Lee YH, Chen YJ, Tsai YS, Kung PT, Chou WY, Tsai WC. Factors influencing the decision to receive total knee replacement among patients with severe knee osteoarthritis under universal health insurance coverage. Sci Rep 2024; 14:30028. [PMID: 39627381 PMCID: PMC11615335 DOI: 10.1038/s41598-024-81852-7] [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: 07/03/2024] [Accepted: 11/29/2024] [Indexed: 12/06/2024] Open
Abstract
This study aimed to investigate the factors influencing the decision of patients with severe knee osteoarthritis, who are covered by universal health insurance, to undergo total knee replacement (TKR) surgery, as recommended by orthopedic physicians. A questionnaire survey was used to collect participants' demographics, socio-economic status, medical history, baseline Oxford Knee Score (OKS), and EuroQol-5 Dimension Questionnaire (EQ-5D). We included 704 patients with severe knee osteoarthritis, of which 487 underwent TKR (surgery group), while 217 did not (non-surgery group). Descriptive statistics was used to compare the characteristics of patients in the two groups, while logistic regression identified the factors influencing patients' choice for TKR. Patients aged 75-79 or older were less likely to undergo TKR; those with poorer OKS (OR = 0.83, 95% CI: 0.79-0.86) and lower EQ-5D VAS scores (OR = 0.97, 95% CI: 0.95-0.99) were more likely to undergo TKR. Household income did not significantly affect the decision of the patients to undergo surgery. In conclusion, for patients with severe knee osteoarthritis, the impact of joint discomfort on function and quality of life is the primary factor influencing their decision to undergo TKR, while economic factors do not have a significant impact under the provision of universal health insurance coverage.
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Affiliation(s)
- Cheng-Chi Wang
- Department of Public Health, China Medical University, Taichung, Taiwan
- Department of Orthopedics, Taichung Veterans General Hospital, Taichung, Taiwan
| | - Kui-Chou Huang
- Department of Orthopedics, Asia University Hospital, Taichung, Taiwan
| | - Ming-Chou Ku
- Department of Orthopedics, Show Chwan Memorial Hospital, Changhua, Taiwan
| | - Chien-Chou Pan
- Department of Orthopedics, Taichung Veterans General Hospital, Taichung, Taiwan
- Department of Rehabilitation Science, Jenteh Junior College of Medicine, Nursing and Management, Miaoli, Taiwan
| | - Cheng-Pu Hsieh
- Department of Orthopedics, Changhua Christian Hospital, Changhua, Taiwan
| | - Ing-Lin Chang
- Department of Orthopedics, Changhua Christian Hospital, Changhua, Taiwan
| | - Chung-Yuh Tzeng
- Department of Orthopedics, Taichung Veterans General Hospital, Taichung, Taiwan
- Department of Rehabilitation Science, Jenteh Junior College of Medicine, Nursing and Management, Miaoli, Taiwan
- Institute of Biomedical Sciences, National Chung Hsing University, Taichung, Taiwan
| | - Chao-Ping Chen
- Department of Public Health, China Medical University, Taichung, Taiwan
- Department of Orthopedics, Taichung Veterans General Hospital, Taichung, Taiwan
- Department of Acupressure Technology, Jenteh Junior College of Medicine, Nursing and Management, Miaoli, Taiwan
| | - Yung-Heng Lee
- Department of Orthopedics, Cishan Hospital, Ministry of Health and Welfare, Kaohsiung, Taiwan
| | - Yen-Jen Chen
- Department of Orthopedics, Asia University Hospital, Taichung, Taiwan
- Department of Medicine, China Medical University, Taichung, Taiwan
- Department of Orthopedics, China Medical University Hospital, Taichung, Taiwan
| | - Yi-Shiun Tsai
- Department of Orthopedics, Feng Yuan Hospital, Ministry of Health and Welfare, Taichung, Taiwan
| | - Pei-Tseng Kung
- Department of Healthcare Administration, Asia University, Taichung, Taiwan
- Department of Medical Research, China Medical University Hospital, China Medical University, Taichung, Taiwan
| | - Wen-Yu Chou
- Department of Health Services Administration, China Medical University, No. 100, Sec. 1, Jingmao Rd., Beitun Dist., Taichung, 406040, Taiwan
| | - Wen-Chen Tsai
- Department of Health Services Administration, China Medical University, No. 100, Sec. 1, Jingmao Rd., Beitun Dist., Taichung, 406040, Taiwan.
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Di Giacomo P, Forte G, Capogna I, Casagrande M, Di Paolo C. The role of nutraceuticals in the management of temporomandibular disorders. JOURNAL OF COMPLEMENTARY & INTEGRATIVE MEDICINE 2024; 21:540-547. [PMID: 38958698 DOI: 10.1515/jcim-2023-0394] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/27/2024] [Accepted: 06/17/2024] [Indexed: 07/04/2024]
Abstract
OBJECTIVES Temporomandibular disorders (TMDs) are usually treated with occlusal appliances and supportive treatments such as physical therapy and drugs. Supplements can be included among potential supportive therapies, with the aim of reducing the use of drugs. To evaluate the efficacy of nutraceuticals' short-term treatment in subjects with temporomandibular disorders. METHODS The study started in January 2021 and ended in January 2022. Subjects with temporomandibular disorders and a verbal numeric scale >40 were recruited and randomly assigned to one of the following groups. If waiting to start a therapy, to the nutraceutical group or to the no treatment group, while if already undergoing splint therapy, to nutraceautical+splint group or to splint therapy group. Nutraceutical used was composed by Boswellia Serrata Casperome, Magnesium, Tryptophan and vitamins B2 and D with a posology of one tablet/day before sleep for 40 days. Presence of temporomandibular pain, headache, neck pain and sleep/emotional disorders were assessed at T0 and at T1, after 40 days. ANOVA was performed to compare treatments with nutraceuticals and their respective controls, as for the variables related to painful symptomatology. Chi-squared was conducted to assess differences in sleep/emotional disorders between groups. The statistical significance was p<0.05. RESULTS The groups using nutraceuticals showed statistically significant improvements over controls for most of the variables analyzed. CONCLUSIONS The use of nutraceutical seems to be a valuable support for TMD therapy in the short term either alone or combined with occlusal splint therapy.
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Affiliation(s)
- Paola Di Giacomo
- Department of Oral and Maxillo-Facial Sciences, 209311 Sapienza University of Rome , Rome, Italy
| | - Giuseppe Forte
- Department of Psychology, 209311 Sapienza University of Rome , Rome, Italy
| | - Irene Capogna
- Department of Oral and Maxillo-Facial Sciences, 209311 Sapienza University of Rome , Rome, Italy
| | - Maria Casagrande
- Department of Psychology, 209311 Sapienza University of Rome , Rome, Italy
| | - Carlo Di Paolo
- Department of Oral and Maxillo-Facial Sciences, 209311 Sapienza University of Rome , Rome, Italy
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Patnaik R, Varghese R, Jannati S, Naidoo N, Banerjee Y. Targeting PAR2-mediated inflammation in osteoarthritis: a comprehensive in vitro evaluation of oleocanthal's potential as a functional food intervention for chondrocyte protection and anti-inflammatory effects. BMC Musculoskelet Disord 2024; 25:769. [PMID: 39354427 PMCID: PMC11446003 DOI: 10.1186/s12891-024-07888-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/26/2024] [Accepted: 09/20/2024] [Indexed: 10/03/2024] Open
Abstract
BACKGROUND Osteoarthritis (OA) is a prevalent degenerative joint disease characterized by chronic inflammation and progressive cartilage degradation, ultimately leading to joint dysfunction and disability. Oleocanthal (OC), a bioactive phenolic compound derived from extra virgin olive oil, has garnered significant attention due to its potent anti-inflammatory properties, which are comparable to those of non-steroidal anti-inflammatory drugs (NSAIDs). This study pioneers the investigation into the effects of OC on the Protease-Activated Receptor-2 (PAR-2) mediated inflammatory pathway in OA, aiming to validate its efficacy as a functional food-based therapeutic intervention. METHODS To simulate cartilage tissue in vitro, human bone marrow-derived mesenchymal stem cells (BMSCs) were differentiated into chondrocytes. An inflammatory OA-like environment was induced in these chondrocytes using lipopolysaccharide (LPS) to mimic the pathological conditions of OA. The therapeutic effects of OC were evaluated by treating these inflamed chondrocytes with various concentrations of OC. The study focused on assessing key inflammatory markers, catabolic enzymes, and mitochondrial function to elucidate the protective mechanisms of OC. Mitochondrial function, specifically mitochondrial membrane potential (ΔΨm), was assessed using Rhodamine 123 staining, a fluorescent dye that selectively accumulates in active mitochondria. The integrity of ΔΨm serves as an indicator of mitochondrial and bioenergetic function. Additionally, Western blotting was employed to analyze protein expression levels, while real-time polymerase chain reaction (RT-PCR) was used to quantify gene expression of inflammatory cytokines and catabolic enzymes. Flow cytometry was utilized to measure cell viability and apoptosis, providing a comprehensive evaluation of OC's therapeutic effects on chondrocytes. RESULTS The results demonstrated that OC significantly downregulated PAR-2 expression in a dose-dependent manner, leading to a substantial reduction in pro-inflammatory cytokines, including TNF-α, IL-1β, and MCP-1. Furthermore, OC attenuated the expression of catabolic markers such as SOX4 and ADAMTS5, which are critically involved in cartilage matrix degradation. Importantly, OC was found to preserve mitochondrial membrane potential (ΔΨm) in chondrocytes subjected to inflammatory stress, as evidenced by Rhodamine 123 staining, indicating a protective effect on cellular bioenergetics. Additionally, OC modulated the Receptor Activator of Nuclear Factor Kappa-Β Ligand (RANKL)/Receptor Activator of Nuclear Factor Kappa-Β (RANK) pathway, suggesting a broader therapeutic action against the multifactorial pathogenesis of OA. CONCLUSIONS This study is the first to elucidate the modulatory effects of OC on the PAR-2 mediated inflammatory pathway in OA, revealing its potential as a multifaceted therapeutic agent that not only mitigates inflammation but also protects cartilage integrity. The preservation of mitochondrial function and modulation of the RANKL/RANK pathway further underscores OC's comprehensive therapeutic potential in counteracting the complex pathogenesis of OA. These findings position OC as a promising candidate for integration into nutritional interventions aimed at managing OA. However, further research is warranted to fully explore OC's therapeutic potential across different stages of OA and its long-term effects in musculoskeletal disorders.
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Laky B, Huemer D, Eigenschink M, Sagl B, Thell R, Wagner KH, Anderl W, Heuberer PR. A Dietary Supplement in the Management of Patients with Lumbar Osteochondrosis: A Randomized, Double-Blinded, Placebo-Controlled Study. Nutrients 2024; 16:2695. [PMID: 39203831 PMCID: PMC11357631 DOI: 10.3390/nu16162695] [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: 07/14/2024] [Revised: 08/07/2024] [Accepted: 08/09/2024] [Indexed: 09/03/2024] Open
Abstract
Various nutritional supplements are available over the counter, yet few have been investigated in randomized controlled trials. The rationale for using the specific mix of nutritional substances including collagen type II, hyaluronic acid, n-acetyl-glucosamine, bamboo extract, L-lysine, and vitamin C is the assumption that combining naturally occurring ingredients of the intervertebral disc would maintain spine function. This double-blinded, placebo-controlled randomized trial aimed to evaluate the efficacy of a nutraceutical supplement mix in the management of lumbar osteochondrosis. Fifty patients were randomly assigned to either the supplement or placebo group in a 1:1 ratio. Patient-Reported Outcome Measures (PROMs) included the Oswestry Disability Index (ODI), the visual analogue scale for pain (pVAS), short form-12 (SF-12) physical and mental component summary subscale scores (PCS and MCS, respectively), and global physical activity questionnaire (GPAQ). Magnetic resonance imaging (MRI) was used to evaluate degenerative changes of intervertebral discs (IVD) including Pfirrmann grades as well as three-dimensional (3D) volume measurements. Data were collected at baseline and after the 3-month intervention. None of the PROMs were significantly different between the supplement and placebo groups. Disc degeneration according to Pfirrmann classifications remained stable during the 3-month intervention in both groups. Despite no significance regarding the distribution of Pfirrmann grade changes (improvement, no change, worsening; p = 0.259), in the supplement group, one patient achieved a three-grade improvement, and worsening of Pfirrmann grades were only detected in the placebo group (9.1%). Furthermore, in-depth evaluations of MRIs showed significantly higher 3D-measured volume changes (increase) in the supplement (+740.3 ± 796.1 mm3) compared to lower 3D-measured volume changes (decrease) in the placebo group (-417.2 ± 875.0 mm3; p < 0.001). In conclusion, this multi-nutrient supplement might not only stabilize the progression of lumbar osteochondrosis, but it might also potentially even increase IVD volumes as detected on MRIs.
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Affiliation(s)
- Brenda Laky
- Austrian Research Group for Regenerative and Orthopedic Medicine (AURROM), 1050 Vienna, Austria; (D.H.); (M.E.); (W.A.); (P.R.H.)
- Austrian Society of Regenerative Medicine (RegMed), 1010 Vienna, Austria
- Faculty of Medicine, Sigmund Freud Private University Medicine, 1020 Vienna, Austria
- Center for Clinical Research, University Clinic of Dentistry, Medical University of Vienna, 1090 Vienna, Austria
- Department of Nutritional Sciences, University of Vienna, 1090 Vienna, Austria;
| | - Daniel Huemer
- Austrian Research Group for Regenerative and Orthopedic Medicine (AURROM), 1050 Vienna, Austria; (D.H.); (M.E.); (W.A.); (P.R.H.)
- Medical University of Vienna, 1090 Vienna, Austria;
| | - Martin Eigenschink
- Austrian Research Group for Regenerative and Orthopedic Medicine (AURROM), 1050 Vienna, Austria; (D.H.); (M.E.); (W.A.); (P.R.H.)
- Department for Trauma and Orthopedic Surgery, AUVA Trauma Center Vienna-Meidling, 1100 Vienna, Austria
| | - Benedikt Sagl
- Competence Center Artificial Intelligence, University Clinic of Dentistry, Medical University of Vienna, 1090 Vienna, Austria;
| | - Rainer Thell
- Medical University of Vienna, 1090 Vienna, Austria;
- Emergency Department, Klinik Donaustadt, 1220 Vienna, Austria
| | - Karl-Heinz Wagner
- Department of Nutritional Sciences, University of Vienna, 1090 Vienna, Austria;
| | - Werner Anderl
- Austrian Research Group for Regenerative and Orthopedic Medicine (AURROM), 1050 Vienna, Austria; (D.H.); (M.E.); (W.A.); (P.R.H.)
- Momentum Praxis Mödling, 2340 Mödling, Austria
| | - Philipp R. Heuberer
- Austrian Research Group for Regenerative and Orthopedic Medicine (AURROM), 1050 Vienna, Austria; (D.H.); (M.E.); (W.A.); (P.R.H.)
- OrthoCare, 1100 Vienna, Austria
- HealthPi Medical Center, 1010 Vienna, Austria
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Chao YM, Wu HY, Yeh SH, Yang DI, Her LS, Wu YL. Glucosamine Enhancement of Learning and Memory Functions by Promoting Fibroblast Growth Factor 21 Production. Int J Mol Sci 2024; 25:4211. [PMID: 38673797 PMCID: PMC11050103 DOI: 10.3390/ijms25084211] [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: 02/05/2024] [Revised: 03/31/2024] [Accepted: 04/03/2024] [Indexed: 04/28/2024] Open
Abstract
Fibroblast growth factor 21 (FGF21) plays a crucial role in metabolism and brain function. Glucosamine (GLN) has been recognized for its diverse beneficial effects. This study aimed to elucidate the modulation of FGF21 production by GLN and its impact on learning and memory functions. Using both in vivo and in vitro models, we investigated the effects of GLN on mice fed with a normal diet or high-fat diet and on mouse HT22 hippocampal cells, STHdhQ7/Q7 striatal cells, and rat primary cortical neurons challenged with GLN. Our results indicated that GLN promotes learning and memory functions in mice and upregulates FGF21 expression in the hippocampus, cortex, and striatum, as well as in HT22 cells, STHdhQ7/Q7 cells, and cortical neurons. In animals receiving GLN together with an FGF21 receptor FGFR1 inhibitor (PD173074), the GLN-enhanced learning and memory functions and induction of FGF21 production in the hippocampus were significantly attenuated. While exploring the underlying molecular mechanisms, the potential involvement of NF-κB, Akt, p38, JNK, PKA, and PPARα in HT22 and NF-κB, Akt, p38, and PPARα in STHdhQ7/Q7 were noted; GLN was able to mediate the activation of p65, Akt, p38, and CREB in HT22 and p65, Akt, and p38 in STHdhQ7/Q7 cells. Our accumulated findings suggest that GLN may increase learning and memory functions by inducing FGF21 production in the brain. This induction appears to be mediated, at least in part, through GLN's activation of the NF-κB, Akt, p38, and PKA/CREB pathways.
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Affiliation(s)
- Yu-Ming Chao
- Institute of Physiology, College of Medicine, National Yang Ming Chiao Tung University, Taipei 112304, Taiwan; (Y.-M.C.); (S.-H.Y.)
| | - Hon-Yen Wu
- Division of Nephrology, Department of Internal Medicine, Far Eastern Memorial Hospital, New Taipei City 220, Taiwan;
- School of Medicine, College of Medicine, National Yang Ming Chiao Tung University, Taipei 112, Taiwan
| | - Sin-Huei Yeh
- Institute of Physiology, College of Medicine, National Yang Ming Chiao Tung University, Taipei 112304, Taiwan; (Y.-M.C.); (S.-H.Y.)
| | - Ding-I Yang
- Institute of Brain Science, College of Medicine, National Yang Ming Chiao Tung University, Taipei 112, Taiwan;
| | - Lu-Shiun Her
- Department of Life Sciences, College of Bioscience and Biotechnology, National Cheng Kung University, Tainan 701, Taiwan;
| | - Yuh-Lin Wu
- Institute of Physiology, College of Medicine, National Yang Ming Chiao Tung University, Taipei 112304, Taiwan; (Y.-M.C.); (S.-H.Y.)
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Lehrer S, Morello T, Karrasch C, Rheinstein PH, Danias J. Effect of Glucosamine on Intraocular Pressure and Risk of Developing Glaucoma. J Glaucoma 2024; 33:240-245. [PMID: 38031296 PMCID: PMC10954404 DOI: 10.1097/ijg.0000000000002340] [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: 05/05/2023] [Accepted: 11/15/2023] [Indexed: 12/01/2023]
Abstract
PRCIS Glucosamine supplementation is common but can be associated with increased intraocular pressure (IOP) and could contribute to the pathogenesis of glaucoma. It may be prudent for ophthalmologists to elicit any history of glucosamine use from their patients and advise them accordingly. Further studies on the role of glucosamine in glaucoma are warranted. BACKGROUND The most frequently recommended slow-acting medication for osteoarthritis symptoms is glucosamine, although its effectiveness is questionable. Widely used glucosamine sulfate supplements may increase IOP. METHODS In the current study, we analyzed online databases such as UK Biobank, MedWatch, and FinnGen to evaluate the relationship between glucosamine and IOP and glaucoma. We included budesonide and fluticasone in the analysis for comparison since these drugs are associated with increased IOP. RESULTS In UK Biobank subjects, glucosamine use was associated with increased corneal compensated IOP ( P =0.002, 2-tailed t test). This was also true in subjects without glaucoma ( P =0.002, 2-tailed t test). However, no significant association between glucosamine and IOP was detected in subjects with a diagnosis of glaucoma. In MedWatch, 0.21% of subjects taking glucosamine reported glaucoma, 0.29% of subjects using budesonide reported glaucoma, and 0.22% of subjects using fluticasone reported glaucoma. In contrast, 0.08% of subjects using any other drug reported glaucoma. This variability is significant ( P <0.001, 2-tailed Fisher exact test). Data from FinnGen on the risk of primary open angle glaucoma or glaucoma in subjects using glucosamine before the diagnosis of the disease revealed a significantly increased risk for both primary open angle glaucoma (hazard ratio: 2.35) and glaucoma (hazard ratio: 1.95). CONCLUSION Glucosamine supplementation is common but can be associated with increased IOP and could contribute to the pathogenesis of glaucoma. It may be prudent for ophthalmologists to elicit any history of glucosamine use from their patients and advise them accordingly. Further studies on the role of glucosamine in glaucoma are warranted.
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Affiliation(s)
- Steven Lehrer
- Department of Radiation Oncology, Icahn School of Medicine at Mount Sinai
| | | | | | | | - John Danias
- Department of Ophthalmology, SUNY Downstate HSU, New York, NY
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Farach-Carson MC, Wu D, França CM. Proteoglycans in Mechanobiology of Tissues and Organs: Normal Functions and Mechanopathology. PROTEOGLYCAN RESEARCH 2024; 2:e21. [PMID: 39584146 PMCID: PMC11584024 DOI: 10.1002/pgr2.21] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/28/2024] [Accepted: 05/03/2024] [Indexed: 11/26/2024]
Abstract
Proteoglycans (PGs) are a diverse class of glycoconjugates that serve critical functions in normal mechanobiology and mechanopathology. Both the protein cores and attached glycosaminoglycan (GAG) chains function in mechanically-sensitive processes, and loss of either can contribute to development of pathological conditions. PGs function as key components of the extracellular matrix (ECM) where they can serve as mechanosensors in mechanosensitive tissues including bone, cartilage, tendon, blood vessels and soft organs. The mechanical properties of these tissues depend on the presence and function of PGs, which play important roles in tissue elasticity, osmolarity and pressure sensing, and response to physical activity. Tissue responses depend on cell surface mechanoreceptors that include integrins, CD44, voltage sensitive ion channels, transient receptor potential (TRP) and piezo channels. PGs contribute to cell and molecular interplay in wound healing, fibrosis, and cancer, where they transduce the mechanical properties of the ECM and influence the progression of various context-specific conditions and diseases. The PGs that are most important in mechanobiology vary depending on the tissue and its functions and functional needs. Perlecan, for example, is important in the mechanobiology of basement membranes, cardiac and skeletal muscle, while aggrecan plays a primary role in the mechanical properties of cartilage and joints. A variety of techniques have been used to study the mechanobiology of PGs, including atomic force microscopy, mouse knockout models, and in vitro cell culture experiments with 3D organoid models. These studies have helped to elucidate the tissue-specific roles that PGs play in cell-level mechanosensing and tissue mechanics. Overall, the study of PGs in mechanobiology is yielding fundamental new concepts in the molecular basis of mechanosensing that can open the door to the development of new treatments for a host of conditions related to mechanopathology.
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Affiliation(s)
- Mary C Farach-Carson
- Department of Diagnostic and Biomedical Sciences, The University of Texas Health Science Center at Houston, School of Dentistry, Houston, TX 77054
- Departments of BioSciences and Bioengineering, Rice University, Houston, TX 77005
| | - Danielle Wu
- Department of Diagnostic and Biomedical Sciences, The University of Texas Health Science Center at Houston, School of Dentistry, Houston, TX 77054
- Departments of BioSciences and Bioengineering, Rice University, Houston, TX 77005
| | - Cristiane Miranda França
- Department of Oral Rehabilitation and Biosciences, School of Dentistry, Oregon Health & Science University, Portland, OR, 97201
- Knight Cancer Precision Biofabrication Hub, Cancer Early Detection Advanced Research Center (CEDAR), Knight Cancer Institute, Oregon Health & Science University, Portland, OR, 97201
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Wang D, Russel WA, Macdonald KM, De Leon VM, Ay A, Belanger KD. Analysis of the gut microbiome in sled dogs reveals glucosamine- and activity-related effects on gut microbial composition. Front Vet Sci 2024; 11:1272711. [PMID: 38384960 PMCID: PMC10879321 DOI: 10.3389/fvets.2024.1272711] [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: 08/04/2023] [Accepted: 01/16/2024] [Indexed: 02/23/2024] Open
Abstract
The composition of the microbiome influences many aspects of physiology and health, and can be altered by environmental factors, including diet and activity. Glucosamine is a dietary supplement often administered to address arthritic symptoms in humans, dogs, and other mammals. To investigate how gut microbial composition varies with glucosamine supplementation, we performed 16S rRNA sequence analysis of fecal samples from 24 Alaskan and Inuit huskies and used mixed effects models to investigate associations with activity, age, and additional factors. Glucosamine ingestion, age, activity, sex, and diet were correlated with differences in alpha-diversity, with diversity decreasing in dogs consuming glucosamine. Beta-diversity analysis revealed clustering of dogs based on glucosamine supplementation status. Glucosamine supplementation and exercise-related activity were associated with greater inter-individual pairwise distances. At the family level, Lactobacillaceae and Anaerovoracaceae relative abundances were lower in supplemented dogs when activity was accounted for. At the genus level, Eubacterium [brachy], Sellimonus, Parvibacter, and an unclassified genus belonging to the same family as Parvibacter (Eggerthellaceae) all were lower in supplemented dogs, but only significantly so post-activity. Our findings suggest that glucosamine supplementation alters microbiome composition in sled dogs, particularly in the context of exercise-related activity.
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Affiliation(s)
- Dong Wang
- Department of Computer Science, Colgate University, Hamilton, NY, United States
- Department of Mathematics, Colgate University, Hamilton, NY, United States
| | - William A. Russel
- Department of Biology, Colgate University, Hamilton, NY, United States
| | | | | | - Ahmet Ay
- Department of Mathematics, Colgate University, Hamilton, NY, United States
- Department of Biology, Colgate University, Hamilton, NY, United States
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11
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Zhang H, Huang J, Alahdal M. Exosomes loaded with chondrogenic stimuli agents combined with 3D bioprinting hydrogel in the treatment of osteoarthritis and cartilage degeneration. Biomed Pharmacother 2023; 168:115715. [PMID: 37857246 DOI: 10.1016/j.biopha.2023.115715] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/09/2023] [Revised: 10/07/2023] [Accepted: 10/11/2023] [Indexed: 10/21/2023] Open
Abstract
Osteoarthritis (OA) is a challenging joint inflammatory disease that often leads to disability. Immunoregulatory Exosomes (Exos) have shown promise in OA and cartilage degeneration treatment. Engineering Exos to deliver therapeutic agents like Kartogenin (KGN) has displayed potential for restoring cartilage regeneration. However, challenges include the uneven distribution of Exos at the injury site and the release of Exos cargo out of chondrocytes. Hydrogel-loaded uMSC-Exo has demonstrated significant therapeutic effects in wound healing and tissue regeneration. Recently, a new version of three-dimensional (3D) bioprinting of hydrogel significantly restored cartilage regeneration in OA joints. Combining immune regulatory Exos with 3D bioprinting hydrogel (3D-BPH-Exos) holds the potential for immunomodulating cartilage tissue and treatment of OA. It can reduce intracellular inflammasome formation and the release of inflammatory agents like IL-1β, TNF-α, and INF-γ, while also preventing chondrocyte apoptosis by restoring mitochondrial functions and enhancing chondrogenesis in synovial MSCs, osteoprogenitor cells, and osteoclasts. Loading Exos with chondrogenic stimuli agents in the 3D-BPH-Exos approach may offer a faster and safer strategy for cartilage repair while better inhibiting joint inflammation than high doses of anti-inflammatory drugs and cell-based therapies. This review provides a comprehensive overview of hydrogel bioprinting and exosome-based therapy in OA. It emphasizes the potential of 3D-BPH-Exos loaded with chondrogenic stimuli agents for OA treatment, serving as a basis for further research.
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Affiliation(s)
- Hui Zhang
- Shenzhen Key Laboratory of Tissue Engineering, Shenzhen Laboratory of Digital Orthopedic Engineering, Shenzhen Second People's Hospital (The First Hospital Affiliated to Shenzhen University, Health Science Center), Shenzhen 518035, China; Department of Orthopedics, Shangrao People's Hospital, Shangrao, Jiangxi, China
| | - Jianghong Huang
- Shenzhen Key Laboratory of Tissue Engineering, Shenzhen Laboratory of Digital Orthopedic Engineering, Shenzhen Second People's Hospital (The First Hospital Affiliated to Shenzhen University, Health Science Center), Shenzhen 518035, China.
| | - Murad Alahdal
- Shenzhen Key Laboratory of Tissue Engineering, Shenzhen Laboratory of Digital Orthopedic Engineering, Shenzhen Second People's Hospital (The First Hospital Affiliated to Shenzhen University, Health Science Center), Shenzhen 518035, China; Johns Hopkins All Children's Hospital, 600 5th St. South, St. Petersburg, FL 33701, USA.
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12
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Gasparella M, Cenzi C, Piccione M, Madia VN, Di Santo R, Tudino V, Artico M, Taurone S, De Ponte C, Costi R, Di Liddo R. Effects of Modified Glucosamine on the Chondrogenic Potential of Circulating Stem Cells under Experimental Inflammation. Int J Mol Sci 2023; 24:10397. [PMID: 37373540 DOI: 10.3390/ijms241210397] [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: 12/24/2022] [Revised: 06/05/2023] [Accepted: 06/16/2023] [Indexed: 06/29/2023] Open
Abstract
Glucosamine (GlcN) is a glycosaminoglycan (GAGs) constituent in connective tissues. It is naturally produced by our body or consumed from diets. In the last decade, in vitro and in vivo trials have demonstrated that the administration of GlcN or its derivates has a protective effect on cartilage when the balance between catabolic and anabolic processes is disrupted and cells are no longer able to fully compensate for the loss of collagen and proteoglycans. To date, these benefits are still controversial because the mechanism of action of GlcN is not yet well clarified. In this study, we have characterized the biological activities of an amino acid (AA) derivate of GlcN, called DCF001, in the growth and chondrogenic induction of circulating multipotent stem cells (CMCs) after priming with tumor necrosis factor-alpha (TNFα), a pleiotropic cytokine commonly expressed in chronic inflammatory joint diseases. In the present work, stem cells were isolated from the human peripheral blood of healthy donors. After priming with TNFα (10 ng/mL) for 3 h, cultures were treated for 24 h with DCF001 (1 μg/mL) dissolved in a proliferative (PM) or chondrogenic (CM) medium. Cell proliferation was analyzed using a Corning® Cell Counter and trypan blue exclusion technique. To evaluate the potentialities of DCF001 in counteracting the inflammatory response to TNFα, we measured the amount of extracellular ATP (eATP) and the expression of adenosine-generating enzymes CD39/CD73, TNFα receptors, and NF-κB inhibitor IκBα using flow cytometry. Finally, total RNA was extracted to perform a gene expression study of some chondrogenic differentiation markers (COL2A1, RUNX2, and MMP13). Our analysis has shed light on the ability of DCF001 to (a) regulate the expression of CD39, CD73, and TNF receptors; (b) modulate eATP under differentiative induction; (c) enhance the inhibitory activity of IκBα, reducing its phosphorylation after TNFα stimulation; and (d) preserve the chondrogenic potentialities of stem cells. Although preliminary, these results suggest that DCF001 could be a valuable supplement for ameliorating the outcome of cartilage repair interventions, enhancing the efficacy of endogenous stem cells under inflammatory stimuli.
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Affiliation(s)
- Marco Gasparella
- Local Health Unit Treviso, Department of Pediatric Surgery, 31100 Treviso, Italy
| | - Carola Cenzi
- Department of Pharmaceutical and Pharmacological Sciences, University of Padova, 35131 Padova, Italy
| | - Monica Piccione
- Department of Pharmaceutical and Pharmacological Sciences, University of Padova, 35131 Padova, Italy
| | - Valentina Noemi Madia
- Department of Drug Chemistry and Technology, University of Rome "La Sapienza", 00185 Rome, Italy
| | - Roberto Di Santo
- Department of Drug Chemistry and Technology, University of Rome "La Sapienza", 00185 Rome, Italy
| | - Valeria Tudino
- Department of Drug Chemistry and Technology, University of Rome "La Sapienza", 00185 Rome, Italy
| | - Marco Artico
- Department of Sensory Organs, University of Rome "La Sapienza", 00185 Rome, Italy
| | - Samanta Taurone
- Department of Movement, Human and Health Sciences-Division of Health Sciences, University of Rome "Foro Italico", 00185 Rome, Italy
| | - Chiara De Ponte
- Department of Sensory Organs, University of Rome "La Sapienza", 00185 Rome, Italy
| | - Roberta Costi
- Department of Drug Chemistry and Technology, University of Rome "La Sapienza", 00185 Rome, Italy
| | - Rosa Di Liddo
- Department of Pharmaceutical and Pharmacological Sciences, University of Padova, 35131 Padova, Italy
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13
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Metabolic Glycoengineering: A Promising Strategy to Remodel Microenvironments for Regenerative Therapy. Stem Cells Int 2023; 2023:1655750. [PMID: 36814525 PMCID: PMC9940976 DOI: 10.1155/2023/1655750] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/07/2022] [Revised: 09/27/2022] [Accepted: 01/17/2023] [Indexed: 02/15/2023] Open
Abstract
Cell-based regenerative therapy utilizes the differentiation potential of stem cells to rejuvenate tissues. But the dynamic fate of stem cells is calling for precise control to optimize their therapeutic efficiency. Stem cell fate is regulated by specific conditions called "microenvironments." Among the various factors in the microenvironment, the cell-surface glycan acts as a mediator of cell-matrix and cell-cell interactions and manipulates the behavior of cells. Herein, metabolic glycoengineering (MGE) is an easy but powerful technology for remodeling the structure of glycan. By presenting unnatural glycans on the surface, MGE provides us an opportunity to reshape the microenvironment and evoke desired cellular responses. In this review, we firstly focused on the determining role of glycans on cellular activity; then, we introduced how MGE influences glycosylation and subsequently affects cell fate; at last, we outlined the application of MGE in regenerative therapy, especially in the musculoskeletal system, and the future direction of MGE is discussed.
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14
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Luo C, Su W, Song Y, Srivastava S. Efficacy and safety of native type II collagen in modulating knee osteoarthritis symptoms: a randomised, double-blind, placebo-controlled trial. J Exp Orthop 2022; 9:123. [PMID: 36562843 PMCID: PMC9780623 DOI: 10.1186/s40634-022-00559-8] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/27/2022] [Accepted: 11/30/2022] [Indexed: 12/24/2022] Open
Abstract
PURPOSE Knee osteoarthritis (OA) is the most common form of clinical arthritis in middle-aged and older individuals. Undenatured or native type II (TII) collagen derived from the chicken sternum has a good therapeutic effect on relieving severe pain of OA. Hence, the present study aimed to investigate the efficacy and safety of TII collagen (Native CT-II®) in individuals with knee OA. METHODS We conducted a 12-week randomised, double-blind, placebo-controlled, parallel-group study on 101 participants aged 40-65 years with knee OA. The participants were randomised to receive either TII collagen, glucosamine hydrochloride + chondroitin sulfate (G + C) or a placebo. The primary outcome was an improvement in the joint health of the participants assessed using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) compared to G + C and placebo. RESULTS Compared with the placebo group (n = 27), the TII collagen group (n = 29) and G + C group (n = 29) significantly improved the overall joint health measured by the change in WOMAC total score (week 12: TII collagen = -32.47 ± 19.51 and G + C = -33.74 ± 24.64 vs. placebo = -13.84 ± 17.61; p < 0.05) and relieved knee joint pain (week 12: TII collagen = -5.69 ± 3.66 and G + C = -6.03 ± 4.72 vs. placebo = -2.71 ± 3.95; p < 0.05). The statistically significant effect was observed as early as 4 weeks after the investigational product administration. Additionally, the TII collagen was more effective in improving the quality of life than the G + C. CONCLUSION TII collagen not only has a significantly better effect and high safety profile for OA but also improves the quality of life of patients. LEVEL OF EVIDENCE Level 1 - Randomized Controlled Trial. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT04470336 ; First submitted date: July 08, 2020; First posted date: July 14, 2020.
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Affiliation(s)
- Cheng Luo
- Research and Development, Jiaxing Hengjie Biopharmaceutical Co. Ltd, No.20 Tongyi Road, Xinfeng Industrial Park, Jiaxing, 314005 Zhejiang China
| | - Weike Su
- grid.469325.f0000 0004 1761 325XDepartment of Pharmacology, Zhejiang University of Technology, Hangzhou, 310023 Zhejiang China
| | - Ying Song
- grid.469325.f0000 0004 1761 325XDepartment of Pharmacology, Zhejiang University of Technology, Hangzhou, 310023 Zhejiang China
| | - Shalini Srivastava
- grid.497496.1Clinical Development, Vedic Lifesciences Pvt. Ltd, 118, Morya House, Off New Link Road, Andheri (West), Mumbai, 400053 Maharashtra India
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15
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Li G, Zhang Z, Ye Y, Li H, Luo H, Tang K, Lai Y. Efficacy, residual effectiveness and safety of diacerein in the treatment of knee osteoarthritis: A meta-analysis of randomized placebo-controlled trials. Medicine (Baltimore) 2022; 101:e31700. [PMID: 36401382 PMCID: PMC9678537 DOI: 10.1097/md.0000000000031700] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/03/2022] Open
Abstract
BACKGROUND Osteoarthritis (OA) is the leading cause of disability in the elderly. Prevention and treatment of OA have become an urgent global demand. The pharmacologic role of diacerein in the treatment of osteoarthritis is controversial. We systematically reviewed the efficacy, safety, and residual effectiveness of diacerein. OBJECTIVES To estimate the symptomatic efficacy, residual effect and safety of diacerein in the treatment of knee osteoarthritis, using a meta-analysis of published randomized controlled trials (RCTs). METHODS On December 1, 2021, we searched PubMed Medline, Web of Science, Cochrane Library databases, Wan Fang Medical Database, and National Knowledge Infrastructure. This study followed the inclusion criteria of the principle P(Population), I(Intervention), C(Comparison), O(Outcome), S (Study design) principle. All studies were randomized controlled trials of knee osteoarthritis. Cochrane bias risk assessment tool was used to assess the risk of bias. Meta-analyses were performed using a random-effects model. To explore sources of heterogeneity, subgroup analysis, sensitivity analysis, regression analysis and publication bias analysis were performed. Drug side effects with complete data were extracted from the included articles and then a combined analysis of these data was performed. RESULTS Eight studies were eligible and were included in our analysis (N = 1277 participants). All studies were randomized controlled trials of knee osteoarthritis. There was no significant difference in reduction of joint pain and improvement of function between diacerein and the control group. However, subgroup analysis suggested, compared with the placebo group, diacerein treatment yielded an improved mean reduction in visual analogue scale score of-0.44% (95% confidence interval [CI]-0.79 to 0.09), an improved the western Ontario and McMaster universities (physical function) score of -0.44% (95% CI-0.72 to -0.12). Follow-up analysis after discontinuation showed that diacerein treatment had a significant residual effect (95% CI-0.81 to- 0.24). Data on drug side effects described in the included articles were extracted for statistical analysis. There was an increased risk of diarrhea with diacerein (Risk Ratio [RR] = 1.95 [1.03 to 2.47]) and withdrawal event from therapy (RR = 0.93 [0.75 to 1.15]). CONCLUSION Diacerein might be considered an effective drug for the treatment of patients with KOA, showing short-term residual effectiveness. Although it is associated with an increased risk of diarrhea, the adverse event is mostly tolerable.
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Affiliation(s)
- Guangting Li
- Department of Hematology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China
- Department of Rheumatology and Immunology, The Fourth Affiliated Hospital of Guangxi Medical University, Liuzhou, Guangxi, China
| | - Zhongming Zhang
- Department of Hematology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China
| | - Yingying Ye
- Department of Joint Osteopathy, The Fourth Affiliated Hospital of Guangxi Medical University, Liuzhou, Guangxi, China
| | - Huiping Li
- Department of Outpatient, Liuzhou People’s Hospital, Liuzhou, Guangxi, China
| | - Hanwen Luo
- Department of Joint Osteopathy, The Fourth Affiliated Hospital of Guangxi Medical University, Liuzhou, Guangxi, China
| | - Kaijiang Tang
- Department of Rheumatology and Immunology, The Fourth Affiliated Hospital of Guangxi Medical University, Liuzhou, Guangxi, China
| | - Yongrong Lai
- Department of Hematology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China
- * Correspondence: Yongrong Lai, Department of Hematology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi 530000, China (e-mail: )
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16
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Shentu CY, Yan G, Xu DC, Chen Y, Peng LH. Emerging pharmaceutical therapeutics and delivery technologies for osteoarthritis therapy. Front Pharmacol 2022; 13:945876. [PMID: 36467045 PMCID: PMC9712996 DOI: 10.3389/fphar.2022.945876] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2022] [Accepted: 11/03/2022] [Indexed: 10/03/2023] Open
Abstract
Osteoarthritis (OA) is one of the most common joint degenerative diseases in the world. At present, the management of OA depends on the lifestyle modification and joint replacement surgery, with the lifespan of prosthesis quite limited yet. Effective drug treatment of OA is essential. However, the current drugs, such as the non-steroidal anti-inflammatory drugs and acetaminophen, as well as glucosamine, chondroitin sulfate, hyaluronic acid, are accompanied by obvious side effects, with the therapeutic efficacy to be enhanced. Recently, novel reagents such as IL-1 antagonists and nerve growth factor inhibitors have entered clinical trials. Moreover, increasing evidence demonstrated that active ingredients of natural plants have great potential for treating OA. Meanwhile, the use of novel drug delivery strategies may overcome the shortcomings of conventional preparations and enhance the bioavailability of drugs, as well as decrease the side effects significantly. This review therefore summarizes the pathological mechanisms, management strategies, and research progress in the drug molecules including the newly identified active ingredient derived from medicinal plants for OA therapy, with the drug delivery technologies also summarized, with the expectation to provide the summary and outlook for developing the next generation of drugs and preparations for OA therapy.
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Affiliation(s)
- Cheng-Yu Shentu
- College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, China
| | - Ge Yan
- College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, China
| | - Dong-Chen Xu
- College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, China
| | - Yong Chen
- College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, China
| | - Li-Hua Peng
- College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, China
- State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Macau, Macau SAR, China
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17
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Conrozier T, Lohse T. Glucosamine as a Treatment for Osteoarthritis: What If It's True? Front Pharmacol 2022; 13:820971. [PMID: 35370756 PMCID: PMC8968913 DOI: 10.3389/fphar.2022.820971] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/23/2021] [Accepted: 02/15/2022] [Indexed: 01/08/2023] Open
Abstract
No disease-modifying treatments are currently available for osteoarthritis (OA). While many therapeutic approaches are now being investigated it is ethical to resort to alternative solutions as that we already possess. There are many reasons for thinking that, at sufficiently high doses, glucosamine (GlcN) sulphate possesses a clinically relevant effect on OA pain. Wide inter-individual variations in the symptomatic effects of GlcN are explained by the extreme variability of its bioavailability. In studies evaluating its structure-modifying effect, GlcN was more effective than placebo in reducing the rate of joint space narrowing in patients with knee OA. More recent data suggest that GlcN may be effective in the primary prevention of OA in sportsmen. There is no controversy concerning the safety of GlcN which does not differ to that of placebo. Several studies have recently revealed an unexpected effect of GlcN on cardiovascular mortality. After adjusting for confounding factors, the regular consumption of GlcN correlated with a 27% reduction in mortality and a 58% reduction in deaths from cardiovascular causes. These data confirm animal studies demonstrating a protective effect of GlcN against cancer and cardiovascular diseases due to modulation of the O-GlcNAcylation pathway. Disorders in O-GlcNAcylation are involved in diabetes, obesity and cancers, which all feature chronic low-grade inflammation (CLGI). By regulating CLGI, GlcN may be beneficial to the symptoms of OA, its outcome and to that of the concomitant chronic pathologies, making GlcN as a valuable candidate for the treatment of OA in patients with metabolic syndrome, diabetes or cardiovascular diseases.
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Affiliation(s)
- Thierry Conrozier
- Department of Rheumatology, Hôpital Nord Franche-Comté, Belfort, France
| | - Thomas Lohse
- Department of Rheumatology, Hôpital Nord Franche-Comté, Belfort, France
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18
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Rayson A, Boudiffa M, Naveed M, Griffin J, Dall’Ara E, Bellantuono I. Geroprotectors and Skeletal Health: Beyond the Headlines. Front Cell Dev Biol 2022; 10:682045. [PMID: 35223825 PMCID: PMC8864221 DOI: 10.3389/fcell.2022.682045] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/17/2021] [Accepted: 01/10/2022] [Indexed: 12/19/2022] Open
Abstract
Osteoporosis and osteoarthritis are the most common age-related diseases of the musculoskeletal system. They are responsible for high level of healthcare use and are often associated with comorbidities. Mechanisms of ageing such as senescence, inflammation and autophagy are common drivers for both diseases and molecules targeting those mechanisms (geroprotectors) have potential to prevent both diseases and their co-morbidities. However, studies to test the efficacy of geroprotectors on bone and joints are scant. The limited studies available show promising results to prevent and reverse Osteoporosis-like disease. In contrast, the effects on the development of Osteoarthritis-like disease in ageing mice has been disappointing thus far. Here we review the literature and report novel data on the effect of geroprotectors for Osteoporosis and Osteoarthritis, we challenge the notion that extension of lifespan correlates with extension of healthspan in all tissues and we highlight the need for more thorough studies to test the effects of geroprotectors on skeletal health in ageing organisms.
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Affiliation(s)
- Alexandra Rayson
- Healthy Lifespan Institute, Department of Oncology and Metabolism, The Medical School, Sheffield, United Kingdom
| | - Maya Boudiffa
- Healthy Lifespan Institute, Department of Oncology and Metabolism, The Medical School, Sheffield, United Kingdom
| | - Maneeha Naveed
- Healthy Lifespan Institute, Department of Oncology and Metabolism, The Medical School, Sheffield, United Kingdom
| | - Jon Griffin
- Healthy Lifespan Institute, Department of Molecular Biology and Biotechnology, The University of Sheffield, Sheffield, United Kingdom
| | - Enrico Dall’Ara
- Healthy Lifespan Institute, Department of Oncology and Metabolism, The Medical School, Sheffield, United Kingdom
- Insigneo Institute for in silico Medicine, Sheffield, United Kingdom
| | - Ilaria Bellantuono
- Healthy Lifespan Institute, Department of Oncology and Metabolism, The Medical School, Sheffield, United Kingdom
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19
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Liu S, Yue H, Ho SL, Kim S, Park JA, Tegafaw T, Ahmad MY, Kim S, Saidi AKAA, Zhao D, Liu Y, Nam SW, Chae KS, Chang Y, Lee GH. Enhanced Tumor Imaging Using Glucosamine-Conjugated Polyacrylic Acid-Coated Ultrasmall Gadolinium Oxide Nanoparticles in Magnetic Resonance Imaging. Int J Mol Sci 2022; 23:1792. [PMID: 35163714 PMCID: PMC8836488 DOI: 10.3390/ijms23031792] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/25/2021] [Revised: 02/01/2022] [Accepted: 02/03/2022] [Indexed: 12/12/2022] Open
Abstract
Owing to a higher demand for glucosamine (GlcN) in metabolic processes in tumor cells than in normal cells (i.e., GlcN effects), tumor imaging in magnetic resonance imaging (MRI) can be highly improved using GlcN-conjugated MRI contrast agents. Here, GlcN was conjugated with polyacrylic acid (PAA)-coated ultrasmall gadolinium oxide nanoparticles (UGONs) (davg = 1.76 nm). Higher positive (brighter or T1) contrast enhancements at various organs including tumor site were observed in human brain glioma (U87MG) tumor-bearing mice after the intravenous injection of GlcN-PAA-UGONs into their tail veins, compared with those obtained with PAA-UGONs as control, which were rapidly excreted through the bladder. Importantly, the contrast enhancements of the GlcN-PAA-UGONs with respect to those of the PAA-UGONs were the highest in the tumor site owing to GlcN effects. These results demonstrated that GlcN-PAA-UGONs can serve as excellent T1 MRI contrast agents in tumor imaging via GlcN effects.
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Affiliation(s)
- Shuwen Liu
- Department of Chemistry, College of Natural Sciences, Kyungpook National University, Taegu 41566, Korea; (S.L.); (H.Y.); (S.L.H.); (T.T.); (M.Y.A.); (A.K.A.A.S.); (D.Z.); (Y.L.)
| | - Huan Yue
- Department of Chemistry, College of Natural Sciences, Kyungpook National University, Taegu 41566, Korea; (S.L.); (H.Y.); (S.L.H.); (T.T.); (M.Y.A.); (A.K.A.A.S.); (D.Z.); (Y.L.)
| | - Son Long Ho
- Department of Chemistry, College of Natural Sciences, Kyungpook National University, Taegu 41566, Korea; (S.L.); (H.Y.); (S.L.H.); (T.T.); (M.Y.A.); (A.K.A.A.S.); (D.Z.); (Y.L.)
| | - Soyeon Kim
- Division of RI-Convergence Research, Korea Institute of Radiological and Medical Sciences (KIRAMS), Seoul 01817, Korea; (S.K.); (J.A.P.)
| | - Ji Ae Park
- Division of RI-Convergence Research, Korea Institute of Radiological and Medical Sciences (KIRAMS), Seoul 01817, Korea; (S.K.); (J.A.P.)
| | - Tirusew Tegafaw
- Department of Chemistry, College of Natural Sciences, Kyungpook National University, Taegu 41566, Korea; (S.L.); (H.Y.); (S.L.H.); (T.T.); (M.Y.A.); (A.K.A.A.S.); (D.Z.); (Y.L.)
| | - Mohammad Yaseen Ahmad
- Department of Chemistry, College of Natural Sciences, Kyungpook National University, Taegu 41566, Korea; (S.L.); (H.Y.); (S.L.H.); (T.T.); (M.Y.A.); (A.K.A.A.S.); (D.Z.); (Y.L.)
| | - Seungho Kim
- Department of Molecular Medicine, School of Medicine, Kyungpook National University, Taegu 41944, Korea; (S.K.); (S.-W.N.)
| | - Abdullah Khamis Ali Al Saidi
- Department of Chemistry, College of Natural Sciences, Kyungpook National University, Taegu 41566, Korea; (S.L.); (H.Y.); (S.L.H.); (T.T.); (M.Y.A.); (A.K.A.A.S.); (D.Z.); (Y.L.)
| | - Dejun Zhao
- Department of Chemistry, College of Natural Sciences, Kyungpook National University, Taegu 41566, Korea; (S.L.); (H.Y.); (S.L.H.); (T.T.); (M.Y.A.); (A.K.A.A.S.); (D.Z.); (Y.L.)
| | - Ying Liu
- Department of Chemistry, College of Natural Sciences, Kyungpook National University, Taegu 41566, Korea; (S.L.); (H.Y.); (S.L.H.); (T.T.); (M.Y.A.); (A.K.A.A.S.); (D.Z.); (Y.L.)
| | - Sung-Wook Nam
- Department of Molecular Medicine, School of Medicine, Kyungpook National University, Taegu 41944, Korea; (S.K.); (S.-W.N.)
| | - Kwon Seok Chae
- Department of Biology Education, Teachers’ College, Kyungpook National University, Taegu 41566, Korea;
| | - Yongmin Chang
- Department of Molecular Medicine, School of Medicine, Kyungpook National University, Taegu 41944, Korea; (S.K.); (S.-W.N.)
| | - Gang Ho Lee
- Department of Chemistry, College of Natural Sciences, Kyungpook National University, Taegu 41566, Korea; (S.L.); (H.Y.); (S.L.H.); (T.T.); (M.Y.A.); (A.K.A.A.S.); (D.Z.); (Y.L.)
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Morris EM, Kitts-Morgan SE, Spangler DM, Ogunade IM, McLeod KR, Harmon DL. Alteration of the Canine Metabolome After a 3-Week Supplementation of Cannabidiol (CBD) Containing Treats: An Exploratory Study of Healthy Animals. Front Vet Sci 2021; 8:685606. [PMID: 34336977 PMCID: PMC8322615 DOI: 10.3389/fvets.2021.685606] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/25/2021] [Accepted: 06/18/2021] [Indexed: 12/21/2022] Open
Abstract
Despite the increased interest and widespread use of cannabidiol (CBD) in humans and companion animals, much remains to be learned about its effects on health and physiology. Metabolomics is a useful tool to evaluate changes in the health status of animals and to analyze metabolic alterations caused by diet, disease, or other factors. Thus, the purpose of this investigation was to evaluate the impact of CBD supplementation on the canine plasma metabolome. Sixteen dogs (18.2 ± 3.4 kg BW) were utilized in a completely randomized design with treatments consisting of control and 4.5 mg CBD/kg BW/d. After 21 d of treatment, blood was collected ~2 h after treat consumption. Plasma collected from samples was analyzed using CIL/LC-MS-based untargeted metabolomics to analyze amine/phenol- and carbonyl-containing metabolites. Metabolites that differed - fold change (FC) ≥ 1.2 or ≤ 0.83 and false discovery ratio (FDR) ≤ 0.05 - between the two treatments were identified using a volcano plot. Biomarker analysis based on receiver operating characteristic (ROC) curves was performed to identify biomarker candidates (area under ROC ≥ 0.90) of the effects of CBD supplementation. Volcano plot analysis revealed that 32 amine/phenol-containing metabolites and five carbonyl-containing metabolites were differentially altered (FC ≥ 1.2 or ≤ 0.83, FDR ≤ 0.05) by CBD; these metabolites are involved in the metabolism of amino acids, glucose, vitamins, nucleotides, and hydroxycinnamic acid derivatives. Biomarker analysis identified 24 amine/phenol-containing metabolites and 1 carbonyl-containing metabolite as candidate biomarkers of the effects of CBD (area under ROC ≥ 0.90; P < 0.01). Results of this study indicate that 3 weeks of 4.5 mg CBD/kg BW/d supplementation altered the canine metabolome. Additional work is warranted to investigate the physiological relevance of these changes.
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Affiliation(s)
- Elizabeth M. Morris
- Department of Animal and Food Sciences, University of Kentucky, Lexington, KY, United States
| | | | - Dawn M. Spangler
- College of Veterinary Medicine, Lincoln Memorial University, Harrogate, TN, United States
| | - Ibukun M. Ogunade
- Division of Animal and Nutritional Science, West Virginia University, Morgantown, WV, United States
| | - Kyle R. McLeod
- Department of Animal and Food Sciences, University of Kentucky, Lexington, KY, United States
| | - David L. Harmon
- Department of Animal and Food Sciences, University of Kentucky, Lexington, KY, United States
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21
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Ammendolia A, Marotta N, Marinaro C, Demeco A, Mondardini P, Costantino C. The synergic use of the High Power Laser Therapy and Glucosamine sulfate in Knee osteoarthritis: A Randomized Controlled Trial. ACTA BIO-MEDICA : ATENEI PARMENSIS 2021; 92:e2021237. [PMID: 34212917 PMCID: PMC8343723 DOI: 10.23750/abm.v92i3.10952] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/14/2020] [Accepted: 11/16/2020] [Indexed: 11/23/2022]
Abstract
Background and aim: To determine the efficacy of the synergistic use of High Power Laser Therapy (HPLT) with glucosamine sulfate (GS) in knee osteoarthritis. Methods: This 2-arm randomized controlled trial (RCT) enrolled 90 subjects (M=53, F=37, y= 55±11.2) and randomly allocated using a stratified sampling method in experimental group (A) with HPLT+GS 1500mg (GS - Dona®, Rottapharm, Monza, Italy) (n=45) or in a control group (B) with HPLT + placebo (n=45). Results: VAS score in Activities of day Living (ADL), Standardized stair climb test (SSCT), Zohlen’s sign (RASPING) and Rabot test were used, to evaluate patients at the beginning of the study (T0), at 2 months (T1) and at 6 months (T2). In the mean scores for VAS in ADL, SSCT, RABOT and RASPING at T1, no significant differences were found between the experimental and the control group with paired T and ANOVA test. But significant differences between groups (p<0.05) in all outcomes were observed at 6 months (T2). Conclusions: HPLT is useful in treating knee osteoarthritis, but when combined with Glucosamine Sulfate, thanks to the synergy of two interventions, can achieve a long-term effect up to 6 months after treatment. (www.actabiomedica.it)
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Affiliation(s)
| | - Nicola Marotta
- Department of Surgical and Medical Sciences, University of Catanzaro "Magna Graecia" Italy.
| | - Cinzia Marinaro
- Department of Surgical and Medical Sciences, University of Catanzaro "Magna Graecia" Italy.
| | - Andrea Demeco
- Department of Surgical and Medical Sciences, University of Catanzaro "Magna Graecia" Italy.
| | | | - Cosimo Costantino
- Department of Medicine and Surgery, University of Parma, Parma, Italy.
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22
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Gani MA, Nurhan AD, Budiatin AS, Siswodihardjo S, Khotib J. Predicting the molecular mechanism of glucosamine in accelerating bone defect repair by stimulating osteogenic proteins. J Basic Clin Physiol Pharmacol 2021; 32:373-377. [PMID: 34214297 DOI: 10.1515/jbcpp-2020-0403] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/26/2020] [Accepted: 01/29/2021] [Indexed: 01/21/2023]
Abstract
OBJECTIVES Bone defect is serious condition that is usually caused by traffic accident. Chitosan is a polymer developed as a scaffold to treat bone defect. However, the mechanism by which chitosan can accelerate bone growth in defect area is still unclear. This study aims to identify proteins which are crucial to the osteogenic properties of chitosan monomer using an in silico study. METHODS Molecular docking was carried out on chitosan monomer, which are d-glucosamine and glucosamine 6-phosphate units against bone morphogenetic protein 2 (BMP-2), fibronectin, fibroblast growth factor (Fgf), and phosphate transporter (PiT) using AutoDock Vina. Ligand preparation was carried out using Chem3D version 15.0.0.106, while protein preparation was performed using AutoDockTools version 1.5.6. RESULTS The results showed that glucosamine 6-phosphate had the best binding affinity with fibronectin and PiT, which was -5.7 kcal mol-1 on both proteins, while d-glucosamine had the best binding affinity with PiT (-5.2 kcal mol-1). CONCLUSIONS This study suggests that the osteogenic properties of chitosan may be due to the presence of bonds between glucosamine units and fibronectin and/or PiT. However, in vitro studies need to be done to prove this.
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Affiliation(s)
- Maria Apriliani Gani
- Department of Clinical Pharmacy, Faculty of Pharmacy, Airlangga University, Surabaya, Indonesia
| | - Ahmad Dzulfikri Nurhan
- Department of Clinical Pharmacy, Faculty of Pharmacy, Airlangga University, Surabaya, Indonesia
| | - Aniek Setiya Budiatin
- Department of Clinical Pharmacy, Faculty of Pharmacy, Airlangga University, Surabaya, Indonesia
| | | | - Junaidi Khotib
- Department of Clinical Pharmacy, Faculty of Pharmacy, Airlangga University, Surabaya, Indonesia
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23
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Moon JM, Finnegan P, Stecker RA, Lee H, Ratliff KM, Jäger R, Purpura M, Slupsky CM, Marco ML, Wissent CJ, Theodosakis J, Kerksick CM. Impact of Glucosamine Supplementation on Gut Health. Nutrients 2021; 13:2180. [PMID: 34202877 PMCID: PMC8308242 DOI: 10.3390/nu13072180] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/20/2021] [Revised: 06/15/2021] [Accepted: 06/22/2021] [Indexed: 11/16/2022] Open
Abstract
Glucosamine (GLU) is a natural compound found in cartilage, and supplementation with glucosamine has been shown to improve joint heath and has been linked to reduced mortality rates. GLU is poorly absorbed and may exhibit functional properties in the gut. The purpose of this study was to examine the impact of glucosamine on gastrointestinal function as well as changes in fecal microbiota and metabolome. Healthy males (n = 6) and females (n = 5) (33.4 ± 7.7 years, 174.1 ± 12.0 cm, 76.5 ± 12.9 kg, 25.2 ± 3.1 kg/m2, n = 11) completed two supplementation protocols that each spanned three weeks separated by a washout period that lasted two weeks. In a randomized, double-blind, placebo-controlled, crossover fashion, participants ingested a daily dose of GLU hydrochloride (3000 mg GlucosaGreen®, TSI Group Ltd., Missoula, MT, USA) or maltodextrin placebo. Study participants completed bowel habit and gastrointestinal symptoms questionnaires in addition to providing a stool sample that was analyzed for fecal microbiota and metabolome at baseline and after the completion of each supplementation period. GLU significantly reduced stomach bloating and showed a trend towards reducing constipation and hard stools. Phylogenetic diversity (Faith's PD) and proportions of Pseudomonadaceae, Peptococcaceae, and Bacillaceae were significantly reduced following GLU consumption. GLU supplementation significantly reduced individual, total branched-chain, and total amino acid excretion, with no glucosamine being detected in any of the fecal samples. GLU had no effect on fecal short-chain fatty acids levels. GLU supplementation provided functional gut health benefits and induced fecal microbiota and metabolome changes.
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Affiliation(s)
- Jessica M. Moon
- Exercise and Performance Nutrition Laboratory, School of Health Sciences, Lindenwood University, St. Charles, MO 63301, USA; (J.M.M.); (R.A.S.); (K.M.R.)
| | - Peter Finnegan
- Department of Food Science & Technology, University of California, Davis, CA 95616, USA; (P.F.); (H.L.); (C.M.S.); (M.L.M.)
| | - Richard A. Stecker
- Exercise and Performance Nutrition Laboratory, School of Health Sciences, Lindenwood University, St. Charles, MO 63301, USA; (J.M.M.); (R.A.S.); (K.M.R.)
| | - Hanna Lee
- Department of Food Science & Technology, University of California, Davis, CA 95616, USA; (P.F.); (H.L.); (C.M.S.); (M.L.M.)
| | - Kayla M. Ratliff
- Exercise and Performance Nutrition Laboratory, School of Health Sciences, Lindenwood University, St. Charles, MO 63301, USA; (J.M.M.); (R.A.S.); (K.M.R.)
| | - Ralf Jäger
- Increnovo, LLC, Milwaukee, WI 53202, USA;
| | - Martin Purpura
- Department of Nutrition, University of California, Davis, CA 95616, USA;
| | - Carolyn M. Slupsky
- Department of Food Science & Technology, University of California, Davis, CA 95616, USA; (P.F.); (H.L.); (C.M.S.); (M.L.M.)
- Department of Nutrition, University of California, Davis, CA 95616, USA;
| | - Maria L. Marco
- Department of Food Science & Technology, University of California, Davis, CA 95616, USA; (P.F.); (H.L.); (C.M.S.); (M.L.M.)
| | | | | | - Chad M. Kerksick
- Exercise and Performance Nutrition Laboratory, School of Health Sciences, Lindenwood University, St. Charles, MO 63301, USA; (J.M.M.); (R.A.S.); (K.M.R.)
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Aljawish A, Chevalot I, Paris C, Muniglia L. Green synthesis of glyco-phenol by enzymatic coupling between ferulic acid and glucosamine: An ecofriendly procedure. Biotechnol Appl Biochem 2021; 69:1438-1450. [PMID: 34155677 DOI: 10.1002/bab.2215] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/27/2020] [Accepted: 06/14/2021] [Indexed: 11/07/2022]
Abstract
A new glyco-phenol was produced by the coupling between glucosamine (Glu) and ferulic acid (FA) using Myceliophthora thermophila laccase as biocatalyst in mild conditions (distilled water and 30°C) as an environmentally friendly process. Results indicated that the enzymatic reaction created a new derivative (FA-Glu), produced from coupling between Glu and FA by covalent bonds. By the high production of (FA-Glu) derivative and its stability, the optimal ratio of (FA:Glu) was of (1:1) at optimal time reaction of 6 h. Under these optimal conditions, almost 55% of -NH2 groups on Glu were bound with FA oxidation products. The new derivative showed higher hydrophobic character than Glu due to the presence of FA in its structure. Liquid chromatography-mass spectrometry analysis showed that (FA-Glu) derivative exhibited a molecular mass at MM 713 g/mol containing one Glu molecule and three FA molecules after decarboxylation. Furthermore, the new derivative presented good antioxidant and antiproliferative activities in comparison with Glu and FA. These results suggest that the enzymatic conjugation between Glu and FA is a promising process to produce a new glyco-phenol having good functional properties for potential applications.
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Affiliation(s)
- Abdulhadi Aljawish
- Laboratory of Biomolecules Engineering (LIBio), Lorraine University, Vandœuvre-lès-Nancy, France
| | - Isabelle Chevalot
- Laboratory of Reactions and Process Engineering (LRGP-UMR 7274), Lorraine University, Vandœuvre-lès-Nancy, France
| | - Cedric Paris
- Laboratory of Biomolecules Engineering (LIBio), Lorraine University, Vandœuvre-lès-Nancy, France
| | - Lionel Muniglia
- Laboratory of Biomolecules Engineering (LIBio), Lorraine University, Vandœuvre-lès-Nancy, France
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25
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Glucosamine and Chondroitin Sulfate: Is There Any Scientific Evidence for Their Effectiveness as Disease-Modifying Drugs in Knee Osteoarthritis Preclinical Studies?-A Systematic Review from 2000 to 2021. Animals (Basel) 2021; 11:ani11061608. [PMID: 34072407 PMCID: PMC8228516 DOI: 10.3390/ani11061608] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/17/2021] [Revised: 05/19/2021] [Accepted: 05/27/2021] [Indexed: 12/19/2022] Open
Abstract
Simple Summary Osteoarthritis is the most common progressive joint disease diagnosed in companion animals and its management continues to be a significant challenge. Nutraceuticals have been widely investigated over the years in the treatment of osteoarthritis and among them, glucosamine and chondroitin sulfate treatments are probably the most common therapies used in veterinary management. However, heterogeneous results were obtained among animal studies and the evidence of their efficacy is still controversial. Animal models have a crucial role in studying the histological changes and evaluating the therapy efficacy of different drugs. Consequently, we consider it may be of interest to evaluate the effectiveness of the most representative nutraceuticals in experimental animal studies of osteoarthritis. In this systematic review, we found a large inconsistency among the experimental protocols, but a positive cartilage response and biochemical modulation were observed in half of the evaluated articles, mainly associated with pre-emptive administrations and with some therapies’ combinations. Even though some of these results were promising, additional data are needed to draw solid conclusions, and further studies evaluating their efficacy in the long term and focusing on other synovial components may be needed to clarify their function. Abstract Glucosamine and chondroitin sulfate have been proposed due to their physiological and functional benefits in the management of osteoarthritis in companion animals. However, the scientific evidence for their use is still controversial. The purpose of this review was to critically elucidate the efficacy of these nutraceutical therapies in delaying the progression of osteoarthritis, evaluating their impact on the synovial knee joint tissues and biochemical markers in preclinical studies by systematically reviewing the last two decades of peer-reviewed publications on experimental osteoarthritis. Three databases (PubMed, Scopus and, Web of Science) were screened for eligible studies. Twenty-two articles were included in the review. Preclinical studies showed a great heterogeneity among the experimental designs and their outcomes. Generally, the evaluated nutraceuticals, alone or in combination, did not seem to prevent the subchondral bone changes, the synovial inflammation or the osteophyte formation. However, further experimental studies may be needed to evaluate their effect at those levels. Regarding the cartilage status and biomarkers, positive responses were identified in approximately half of the evaluated articles. Furthermore, beneficial effects were associated with the pre-emptive administrations, higher doses and, multimodality approaches with some combined therapies. However, additional studies in the long term and with good quality and systematic design are required.
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26
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Clayton P, Hill M, Bogoda N, Subah S, Venkatesh R. Palmitoylethanolamide: A Natural Compound for Health Management. Int J Mol Sci 2021; 22:5305. [PMID: 34069940 PMCID: PMC8157570 DOI: 10.3390/ijms22105305] [Citation(s) in RCA: 68] [Impact Index Per Article: 17.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/01/2021] [Revised: 04/06/2021] [Accepted: 05/06/2021] [Indexed: 01/23/2023] Open
Abstract
All nations which have undergone a nutrition transition have experienced increased frequency and falling latency of chronic degenerative diseases, which are largely driven by chronic inflammatory stress. Dietary supplementation is a valid strategy to reduce the risk and severity of such disorders. Palmitoylethanolamide (PEA) is an endocannabinoid-like lipid mediator with extensively documented anti-inflammatory, analgesic, antimicrobial, immunomodulatory and neuroprotective effects. It is well tolerated and devoid of side effects in animals and humans. PEA's actions on multiple molecular targets while modulating multiple inflammatory mediators provide therapeutic benefits in many applications, including immunity, brain health, allergy, pain modulation, joint health, sleep and recovery. PEA's poor oral bioavailability, a major obstacle in early research, has been overcome by advanced delivery systems now licensed as food supplements. This review summarizes the functionality of PEA, supporting its use as an important dietary supplement for lifestyle management.
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Affiliation(s)
- Paul Clayton
- Institute of Food, Brain and Behaviour, Beaver House, 23-28 Hythe Bridge Street, Oxford OX1 2EP, UK
| | - Mariko Hill
- Gencor Pacific Limited, Discovery Bay, Lantau Island, New Territories, Hong Kong, China; (M.H.); (N.B.); (S.S.)
| | - Nathasha Bogoda
- Gencor Pacific Limited, Discovery Bay, Lantau Island, New Territories, Hong Kong, China; (M.H.); (N.B.); (S.S.)
| | - Silma Subah
- Gencor Pacific Limited, Discovery Bay, Lantau Island, New Territories, Hong Kong, China; (M.H.); (N.B.); (S.S.)
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27
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Vannabouathong C, Zhu M, Chang Y, Bhandari M. Can Medical Cannabis Therapies be Cost-Effective in the Non-Surgical Management of Chronic Knee Pain? CLINICAL MEDICINE INSIGHTS-ARTHRITIS AND MUSCULOSKELETAL DISORDERS 2021; 14:11795441211002492. [PMID: 33795939 PMCID: PMC7970188 DOI: 10.1177/11795441211002492] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 09/30/2020] [Accepted: 02/18/2021] [Indexed: 11/15/2022]
Abstract
Introduction: Chronic knee pain is a common musculoskeletal condition, which usually leads
to decreased quality of life and a substantial financial burden. Various
non-surgical treatments have been developed to relieve pain, restore
function and delay surgical intervention. Research on the benefits of
medical cannabis (MC) is emerging supporting its use for chronic pain
conditions. The purpose of this study was to evaluate the cost-effectiveness
of MC compared to current non-surgical therapies for chronic knee pain
conditions. Methods: We conducted a cost-utility analysis from a Canadian, single payer
perspective and compared various MC therapies (oils, soft gels and dried
flowers at different daily doses) to bracing, glucosamine,
pharmaceutical-grade chondroitin oral non-steroidal anti-inflammatory drugs
(NSAIDs), and opioids. We estimated the quality-adjusted life years (QALYs)
gained with each treatment over 1 year and calculated incremental
cost-utility ratios (ICURs) using both the mean and median estimates for
costs and utilities gained across the range of reported values. The final
ICURs were compared to willingness-to-pay (WTP) thresholds of $66 714,
$133 428 and $200 141 Canadian dollars (CAD) per QALY gained. Results: Regardless of the estimates used (mean or median), both MC oils and soft gels
at both the minimal and maximal recommended daily doses were cost-effective
compared to all current knee pain therapies at the lowest WTP threshold.
Dried flowers were only cost-effective up to a certain dosage (0.75 and
1 g/day based on mean and median estimates, respectively), but all dosages
were cost-effective when the WTP was increased to $133 428/QALY gained. Conclusion: Our study showed that MC may be a cost-effective strategy in the management
of chronic knee pain; however, the evidence on the medical use of cannabis
is limited and predominantly low-quality. Additional trials on MC are
definitely needed, specifically in patients with chronic knee pain.
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Affiliation(s)
| | - Meng Zhu
- OrthoEvidence, Burlington, ON, Canada
| | | | - Mohit Bhandari
- OrthoEvidence, Burlington, ON, Canada.,Department of Surgery, McMaster University, Hamilton, Ontario, Canada
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28
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Xiao S, Lin Y, Tang Y, Lv Z, Chen L. Real-Time Quantification of Cartilage Degeneration by GAG-Targeted Cationic Nanoparticles for Efficient Therapeutic Monitoring in Living Mice. Mol Pharm 2021; 18:1444-1454. [PMID: 33538605 DOI: 10.1021/acs.molpharmaceut.0c01254] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
One of the characterizations of degenerative cartilage disease is the progressive loss of glycosaminoglycans (GAGs). The real-time imaging method to quantify GAGs is of great significance for the biochemical analysis of cartilage and diagnosis and therapeutic monitoring of cartilage degeneration in vivo. To this end, a cationic photoacoustic (PA) contrast agent, poly-l-lysine melanin nanoparticles (PLL-MNPs), specifically targeting anionic GAGs was developed in this study to investigate whether it can image cartilage degeneration. PLL-MNP assessed GAG depletion by Chondroitinase ABC in vitro rat cartilage and intact ex vivo mouse knee joint. A papain-induced cartilage degenerative mice model was used for in vivo photoacoustic imaging (PAI). Oral cartilage supplement glucosamine sulfate was intragastrically administered for mice cartilage repair and the therapeutic efficacy was monitored by PLL-MNP-enhanced PAI. Histologic findings were used to further confirm PAI results. In vitro results revealed that the PLL-MNPs not only had a high binding ability with GAGs but also sensitively monitored GAG content changes by PAI. The PA signal was gradually weakened along with the depletion of GAGs in cartilage. Particularly, PLL-MNPs depicted the cartilage structure and the distribution of GAGs was demonstrated in PA images in ex vivo joints. Compared with the normal joint, a lower signal intensity was detected from degenerative joint at 3 weeks after papain injection, suggesting an early diagnosis of cartilage lesion by PLL-MNPs. Importantly, this PA-enhanced nanoprobe was suitable for monitoring in vivo efficacy of glucosamine sulfate, which effectively blocked cartilage degradation in a high dose manner. In vivo imaging findings correlated well with histological examinations. PLL-MNPs provided sensitive visualization of cartilage degeneration and promising monitoring of therapeutic response in living subjects.
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Affiliation(s)
- Shuyi Xiao
- Department of Orthopedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou 325000, P. R. China.,Department of Pharmacy, The Second Affiliated Hospital and Yuying Children's, Wenzhou 325027, P. R. China
| | - Yimu Lin
- Department of Orthopedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou 325000, P. R. China
| | - Yufu Tang
- Key Laboratory of Flexible Electronics (KLOFE), Institute of Advanced Materials (IAM), Jiangsu National Synergetic Innovation Center for Advanced Materials (SICAM), Nanjing Tech University (NanjingTech), Nanjing 211816, P. R. China
| | - Zhuang Lv
- Department of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Hung Hom, Hong Kong 999077, P. R. China
| | - Liang Chen
- Department of Orthopedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou 325000, P. R. China
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Chen TY, Sun D, Lin WS, Lin YL, Chao YM, Chen SY, Chen YR, Wu YL. Glucosamine regulation of fibroblast growth factor 21 expression in liver and adipose tissues. Biochem Biophys Res Commun 2020; 529:714-719. [PMID: 32736697 DOI: 10.1016/j.bbrc.2020.06.070] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/11/2020] [Accepted: 06/15/2020] [Indexed: 10/23/2022]
Abstract
Obesity is associated with metabolic disorders. Fibroblast growth factor 21 (FGF21) has been recognized as important in metabolism. Glucosamine (GLN) has been demonstrated to perform diverse beneficial functions. This study aimed to reveal whether and how GLN would modulate FGF21 production in relation to metabolism. With in vivo model of normal diet (ND) and high-fat diet (HFD) mice receiving GLN injection and in vitro model of mouse AML12 liver cells and differentiated 3T3L1 adipocytes challenged with GLN, GLN appeared to improve the glucose metabolism in HFD and ND mice and to elevate FGF21 protein expression in HFD liver and to increase both FGF21 protein and mRNA levels in WAT from HFD and ND mice and it also upregulated FGF21 expression in both AML12 and differentiated 3T3L1 cells. By using inhibitors against various signaling pathways, p38, Akt, NF-κB, and PKA appeared potentially involved in GLN-mediated FGF21 production in AML12 cells; GLN was able to mediate activation of NF-κB, p38 or PKA/CREB signaling. Our accumulated findings suggest that GLN may potentially improve the metabolic performance by inducing FGF21 production in liver and adipose tissues and such induction in liver cells may act in part due to GLN induction of the NF-κB, p38 and PKA pathways.
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Affiliation(s)
- Ting-Yu Chen
- Department of Physiology, School of Medicine, National Yang-Ming University, Taipei, Taiwan
| | - David Sun
- Department of Obstetrics and Gynecology, Cheng Hsin General Hospital, Taipei, Taiwan
| | - Wei-Shen Lin
- Department of Physiology, School of Medicine, National Yang-Ming University, Taipei, Taiwan
| | - Yi-Ling Lin
- Department of Physiology, School of Medicine, National Yang-Ming University, Taipei, Taiwan
| | - Yu-Ming Chao
- Department of Physiology, School of Medicine, National Yang-Ming University, Taipei, Taiwan
| | - Shan-Yu Chen
- Department of Physiology, School of Medicine, National Yang-Ming University, Taipei, Taiwan
| | - Yun-Ru Chen
- Department of Physiology, School of Medicine, National Yang-Ming University, Taipei, Taiwan
| | - Yuh-Lin Wu
- Department of Physiology, School of Medicine, National Yang-Ming University, Taipei, Taiwan.
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Variation in Plasma Levels of Glucosamine With Chronic Dosing: A Possible Reason for Inconsistent Clinical Outcomes in Osteoarthritis. Clin Ther 2020; 42:e140-e149. [PMID: 32713600 DOI: 10.1016/j.clinthera.2020.06.009] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/08/2020] [Revised: 05/14/2020] [Accepted: 06/18/2020] [Indexed: 01/23/2023]
Abstract
PURPOSE Glucosamine is widely used by patients with osteoarthritis (OA) to provide symptomatic relief and to delay disease progression. However, clinical studies have reported inconsistent clinical outcomes. The current study hypothesized that the reported inconsistent clinical results could be, in part, due to variable bioavailability and elimination of glucosamine. This study therefore aimed to determine steady-state minimum plasma concentrations (Css min) of glucosamine to examine the variability among patients taking the supplement. METHODS Patients with OA who had been taking glucosamine for at least 1 week were recruited. Patients' blood samples were collected 24 h after the ingestion of the previous dose to determine Observed Css min and after a 5-day washout period to determine the endogenous glucosamine levels (GlcNend). The Actual Css min was calculated by using the following equation: Actual Css min = Observed Css min - GlcNend. The glucosamine plasma concentrations were determined by using a previously developed HPLC method. FINDINGS Ninety-one participants (age range, 42-89 years; mean [SD] age, 68.2 [7.6] years) were recruited (70% females). There was substantial (106-fold) variation, with a 45% coefficient of variation, between the Actual Css min levels (3-320 ng/mL) in participants. No significant association of Actual Css min was observed with various dose- and patient-related variables. IMPLICATIONS The observed high variability in steady-state plasma concentrations indicates substantial inter-patient differences in the absorption and elimination of glucosamine, which could be a cause for inconsistent clinical outcomes in patients with OA.
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Mohammadinejad R, Ashrafizadeh M, Pardakhty A, Uzieliene I, Denkovskij J, Bernotiene E, Janssen L, Lorite GS, Saarakkala S, Mobasheri A. Nanotechnological Strategies for Osteoarthritis Diagnosis, Monitoring, Clinical Management, and Regenerative Medicine: Recent Advances and Future Opportunities. Curr Rheumatol Rep 2020; 22:12. [PMID: 32248371 PMCID: PMC7128005 DOI: 10.1007/s11926-020-0884-z] [Citation(s) in RCA: 43] [Impact Index Per Article: 8.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
PURPOSE OF REVIEW In this review article, we discuss the potential for employing nanotechnological strategies for the diagnosis, monitoring, and clinical management of osteoarthritis (OA) and explore how nanotechnology is being integrated rapidly into regenerative medicine for OA and related osteoarticular disorders. RECENT FINDINGS We review recent advances in this rapidly emerging field and discuss future opportunities for innovations in enhanced diagnosis, prognosis, and treatment of OA and other osteoarticular disorders, the smart delivery of drugs and biological agents, and the development of biomimetic regenerative platforms to support cell and gene therapies for arresting OA and promoting cartilage and bone repair. Nanotubes, magnetic nanoparticles, and other nanotechnology-based drug and gene delivery systems may be used for targeting molecular pathways and pathogenic mechanisms involved in OA development. Nanocomposites are also being explored as potential tools for promoting cartilage repair. Nanotechnology platforms may be combined with cell, gene, and biological therapies for the development of a new generation of future OA therapeutics. Graphical Abstract.
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Affiliation(s)
- Reza Mohammadinejad
- Pharmaceutics Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman, Iran
| | - Milad Ashrafizadeh
- Department of Basic Science, Faculty of Veterinary Medicine, University of Tabriz, Tabriz, Iran
| | - Abbas Pardakhty
- Pharmaceutics Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman, Iran
| | - Ilona Uzieliene
- Department of Regenerative Medicine, State Research Institute Centre for Innovative Medicine, Santariskiu 5, LT-08406, Vilnius, Lithuania
| | - Jaroslav Denkovskij
- Department of Regenerative Medicine, State Research Institute Centre for Innovative Medicine, Santariskiu 5, LT-08406, Vilnius, Lithuania
| | - Eiva Bernotiene
- Department of Regenerative Medicine, State Research Institute Centre for Innovative Medicine, Santariskiu 5, LT-08406, Vilnius, Lithuania
| | - Lauriane Janssen
- Microelectronics Research Unit, Faculty of Information Technology and Electrical Engineering, University of Oulu, PL 4500, 3FI-90014, Oulu, Finland
| | - Gabriela S Lorite
- Microelectronics Research Unit, Faculty of Information Technology and Electrical Engineering, University of Oulu, PL 4500, 3FI-90014, Oulu, Finland
| | - Simo Saarakkala
- Department of Diagnostic Radiology, Oulu University Hospital, Oulu, Finland
- Research Unit of Medical Imaging, Physics and Technology, Faculty of Medicine, University of Oulu, Oulu, Finland
| | - Ali Mobasheri
- Department of Regenerative Medicine, State Research Institute Centre for Innovative Medicine, Santariskiu 5, LT-08406, Vilnius, Lithuania.
- Department of Diagnostic Radiology, Oulu University Hospital, Oulu, Finland.
- Research Unit of Medical Imaging, Physics and Technology, Faculty of Medicine, University of Oulu, Oulu, Finland.
- Centre for Sport, Exercise and Osteoarthritis Versus Arthritis, Queen's Medical Centre, Nottingham, UK.
- Sheik Salem Bin Mahfouz Scientific Chair for Treatment of Osteoarthritis with Stem Cells, King AbdulAziz University, Jeddah, Saudi Arabia.
- University Medical Center Utrecht, Department of Orthopedics and Department of Rheumatology & Clinical Immunology, 508 GA, Utrecht, The Netherlands.
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Multifaceted Protective Role of Glucosamine against Osteoarthritis: Review of Its Molecular Mechanisms. Sci Pharm 2019. [DOI: 10.3390/scipharm87040034] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022] Open
Abstract
Osteoarthritis (OA) is a joint disease resulting from cartilage degeneration and causing joint pain and stiffness. Glucosamine exerts chondroprotective effects and effectively reduces OA pain and stiffness. This review aims to summarise the mechanism of glucosamine in protecting joint health and preventing OA by conducting a literature search on original articles. Current evidence has revealed that glucosamine exhibits anti-inflammatory effects by reducing the levels of pro-inflammatory factors (such as tumour necrosis factor-alpha, interleukin-1, and interleukin-6) and enhancing the synthesis of proteoglycans that retard cartilage degradation and improve joint function. Additionally, glucosamine improves cellular redox status, reduces OA-mediated oxidative damages, scavenges free radicals, upregulates antioxidant proteins and enzyme levels, inhibits the production of reactive oxygen species, and induces autophagy to delay OA pathogenesis. In conclusion, glucosamine prevents OA and maintains joint health by reducing inflammation, improving the redox status, and inducing autophagy in joints. Further studies are warranted to determine the synergistic effect of glucosamine with other anti-inflammatory and/or antioxidative agents on joint health in humans.
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Cordaro M, Siracusa R, Impellizzeri D, D' Amico R, Peritore AF, Crupi R, Gugliandolo E, Fusco R, Di Paola R, Schievano C, Cuzzocrea S. Safety and efficacy of a new micronized formulation of the ALIAmide palmitoylglucosamine in preclinical models of inflammation and osteoarthritis pain. Arthritis Res Ther 2019; 21:254. [PMID: 31779692 PMCID: PMC6883534 DOI: 10.1186/s13075-019-2048-y] [Citation(s) in RCA: 44] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/28/2019] [Accepted: 11/01/2019] [Indexed: 12/21/2022] Open
Abstract
Background Osteoarthritis is increasingly recognized as the result of a complex interplay between inflammation, chrondrodegeneration, and pain. Joint mast cells are considered to play a key role in orchestrating this detrimental triad. ALIAmides down-modulate mast cells and more generally hyperactive cells. Here we investigated the safety and effectiveness of the ALIAmide N-palmitoyl-d-glucosamine (PGA) in inflammation and osteoarthritis pain. Methods Acute toxicity of micronized PGA (m-PGA) was assessed in rats following OECD Guideline No.425. PGA and m-PGA (30 mg/kg and 100 mg/kg) were orally administered to carrageenan (CAR)-injected rats. Dexamethasone 0.1 mg/kg was used as reference. Paw edema and thermal hyperalgesia were measured up to 6 h post-injection, when also myeloperoxidase activity and histological inflammation score were assessed. Rats subjected to intra-articular injection of sodium monoiodoacetate (MIA) were treated three times per week for 21 days with PGA or m-PGA (30 mg/kg). Mechanical allodynia and motor function were evaluated at different post-injection time points. Joint histological and radiographic damage was scored, articular mast cells were counted, and macrophages were immunohistochemically investigated. Levels of TNF-α, IL-1β, NGF, and MMP-1, MMP-3, and MMP-9 were measured in serum using commercial colorimetric ELISA kits. One- or two-way ANOVA followed by a Bonferroni post hoc test for multiple comparisons was used. Results Acute oral toxicity of m-PGA resulted in LD50 values in excess of 2000 mg/kg. A single oral administration of PGA and m-PGA significantly reduced CAR-induced inflammatory signs (edema, inflammatory infiltrate, and hyperalgesia), and m-PGA also reduced the histological score. Micronized PGA resulted in a superior activity to PGA on MIA-induced mechanical allodynia, locomotor disability, and histologic and radiographic damage. The MIA-induced increase in mast cell count and serum level of the investigated markers was also counteracted by PGA and to a significantly greater extent by m-PGA. Conclusions The results of the present study showed that PGA is endorsed with anti-inflammatory, pain-relieving, and joint-protective effects. Moreover, it proved that particle size reduction greatly enhances the activity of PGA, particularly on joint pain and disability. Given these results, m-PGA could be considered a valuable option in the management of osteoarthritis.
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Affiliation(s)
- Marika Cordaro
- Department of Chemical, Biological, Pharmaceutical and Environmental Science, University of Messina, Messina, Italy
| | - Rosalba Siracusa
- Department of Chemical, Biological, Pharmaceutical and Environmental Science, University of Messina, Messina, Italy
| | - Daniela Impellizzeri
- Department of Chemical, Biological, Pharmaceutical and Environmental Science, University of Messina, Messina, Italy
| | - Ramona D' Amico
- Department of Chemical, Biological, Pharmaceutical and Environmental Science, University of Messina, Messina, Italy
| | - Alessio Filippo Peritore
- Department of Chemical, Biological, Pharmaceutical and Environmental Science, University of Messina, Messina, Italy
| | - Rosalia Crupi
- Department of Chemical, Biological, Pharmaceutical and Environmental Science, University of Messina, Messina, Italy
| | - Enrico Gugliandolo
- Department of Chemical, Biological, Pharmaceutical and Environmental Science, University of Messina, Messina, Italy
| | - Roberta Fusco
- Department of Chemical, Biological, Pharmaceutical and Environmental Science, University of Messina, Messina, Italy
| | - Rosanna Di Paola
- Department of Chemical, Biological, Pharmaceutical and Environmental Science, University of Messina, Messina, Italy
| | - Carlo Schievano
- Innovative Statistical Research srl, Prato Della Valle 24, I-35123, Padova, Italy
| | - Salvatore Cuzzocrea
- Department of Chemical, Biological, Pharmaceutical and Environmental Science, University of Messina, Messina, Italy. .,Department of Pharmacological and Physiological Science, Saint Louis University School of Medicine, Saint Louis, USA.
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Hoban C, Byard R, Musgrave I. Hypersensitive adverse drug reactions to glucosamine and chondroitin preparations in Australia between 2000 and 2011. Postgrad Med J 2019; 96:190-193. [DOI: 10.1136/postgradmedj-2019-136957] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/17/2019] [Revised: 09/17/2019] [Accepted: 09/30/2019] [Indexed: 01/01/2023]
Abstract
Purpose of the studyThis study investigates spontaneous adverse drug reactions (ADRs) to glucosamine and chondroitin in the Australian population between 2000 and 2011, with a primary focus on hypersensitivity reactions.Study designCase reports of ADR to glucosamine and chondroitin sent to the Therapeutic Goods Administration between 2000 and 2011 were obtained and analysed. The demographic information and severity of the ADR were recorded for individual ADR cases. These reactions were classified according to the Brown et al grading system for generalised hypersensitivity reactions. This included mild hypersensitivity reactions (generalised erythema, urticaria and angioedema) through to moderate hypersensitivity reactions (wheeze, nausea, vomiting, dizziness (presyncope), diaphoresis, chest or throat tightness and abdominal pain), and more severe reactions (hypotension, confusion and collapse).ResultsIn this study of 366 ADRs to glucosamine and chondroitin preparations, 71.85% of cases (n=263) were found to have hypersensitivity reactions. Of these 263 cases, 92 cases were classified as mild (eg, pruritus, urticaria and lip oedema), 128 cases classified as moderate (such as dyspnoea, nausea and abdominal pain), and 43 cases classified as severe (including amnesia, gait disturbance, somnolence and hypotension). It is not clear whether the patients involved had a known shellfish allergy or underlying atopy.ConclusionResults of this investigation support the need for clear labelling on glucosamine and chondroitin preparations to raise awareness of possible adverse events for those predisposed to allergy or atopy in response to shellfish.
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The effectiveness of treatments for Kashin–Beck disease: a systematic review and network meta-analysis. Clin Rheumatol 2019; 38:3595-3607. [DOI: 10.1007/s10067-019-04704-0] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/20/2019] [Revised: 07/08/2019] [Accepted: 07/17/2019] [Indexed: 12/14/2022]
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Suo H, Li L, Zhang C, Yin J, Xu K, Liu J, Fu J. Glucosamine‐grafted methacrylated gelatin hydrogels as potential biomaterials for cartilage repair. J Biomed Mater Res B Appl Biomater 2019; 108:990-999. [DOI: 10.1002/jbm.b.34451] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2019] [Revised: 06/09/2019] [Accepted: 07/11/2019] [Indexed: 11/11/2022]
Affiliation(s)
- Hairui Suo
- The State Key Laboratory of Fluid Power and Mechatronic Systems, School of Mechanical EngineeringZhejiang University Hangzhou China
- Key Laboratory of 3D Printing Process and Equipment of Zhejiang Province, School of Mechanical EngineeringZhejiang University Hangzhou China
- School of AutomationHangzhou Dianzi University Hangzhou China
| | - Liang Li
- Department of OrthopedicsNo. 906 Hospital of People's Liberation Army Ningbo China
| | - Chuanxin Zhang
- Adult Joint Reconstruction and Sports Medicine Center, Department of Orthopaedics, Changzheng HospitalSecond Military Medical University Shanghai China
| | - Jun Yin
- The State Key Laboratory of Fluid Power and Mechatronic Systems, School of Mechanical EngineeringZhejiang University Hangzhou China
- Key Laboratory of 3D Printing Process and Equipment of Zhejiang Province, School of Mechanical EngineeringZhejiang University Hangzhou China
| | - Kedi Xu
- Qiushi Academy for Advanced Studies (QAAS)Zhejiang University Hangzhou China
- Department of Biomedical Engineering, Key Laboratory of Biomedical Engineering of Education MinistryZhejiang University Hangzhou China
| | - Jingyi Liu
- The State Key Laboratory of Fluid Power and Mechatronic Systems, School of Mechanical EngineeringZhejiang University Hangzhou China
- Key Laboratory of 3D Printing Process and Equipment of Zhejiang Province, School of Mechanical EngineeringZhejiang University Hangzhou China
| | - Jianzhong Fu
- The State Key Laboratory of Fluid Power and Mechatronic Systems, School of Mechanical EngineeringZhejiang University Hangzhou China
- Key Laboratory of 3D Printing Process and Equipment of Zhejiang Province, School of Mechanical EngineeringZhejiang University Hangzhou China
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Cheki M, Jafari S, Najafi M, Mahmoudzadeh A. Glucosamine Protects Rat Bone Marrow Cells Against Cisplatin-induced Genotoxicity and Cytotoxicity. Anticancer Agents Med Chem 2019; 19:1695-1702. [PMID: 31272360 DOI: 10.2174/1871520619666190704164126] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/05/2019] [Revised: 05/20/2019] [Accepted: 05/21/2019] [Indexed: 12/22/2022]
Abstract
BACKGROUND AND OBJECTIVE Glucosamine is a widely prescribed dietary supplement used in the treatment of osteoarthritis. In the present study, the chemoprotectant ability of glucosamine was evaluated against cisplatin-induced genotoxicity and cytotoxicity in rat bone marrow cells. METHODS Glucosamine was orally administrated to rats at doses of 75 and 150 mg/kg body weight for seven consecutive days. On the seventh day, the rats were treated with a single injection of cisplatin (5 mg/kg, i.p.) at 1h after the last oral administration. The cisplatin antagonistic potential of glucosamine was assessed by micronucleus assay, Reactive Oxygen Species (ROS) level analysis, hematological analysis, and flow cytometry. RESULTS Glucosamine administration to cisplatin-treated rats significantly decreased the frequencies of Micronucleated Polychromatic Erythrocytes (MnPCEs) and Micronucleated Normchromatic Erythrocytes (MnNCEs), and also increased PCE/(PCE+NCE) ratio in bone marrow cells. Furthermore, treatment of rats with glucosamine before cisplatin significantly inhibited apoptosis, necrosis and ROS generation in bone marrow cells, and also increased red blood cells count in peripheral blood. CONCLUSION This study shows glucosamine to be a new effective chemoprotector against cisplatin-induced DNA damage and apoptosis in rat bone marrow cells. The results of this study may be helpful in reducing the harmful effects of cisplatin-based chemotherapy in the future.
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Affiliation(s)
- Mohsen Cheki
- Cellular and Molecular Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| | - Salman Jafari
- Department of Radiology Technology, School of Paramedicine, Hamadan University of Medical Sciences, Hamadan, Iran
| | - Masoud Najafi
- Radiology and Nuclear Medicine Department, School of Paramedical Sciences, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Aziz Mahmoudzadeh
- Department of Biosciences and Biotechnology, Malek-Ashtar University of Technology, Tehran, Iran
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Lewis R, Gómez Álvarez CB, Rayman M, Lanham-New S, Woolf A, Mobasheri A. Strategies for optimising musculoskeletal health in the 21 st century. BMC Musculoskelet Disord 2019; 20:164. [PMID: 30971232 PMCID: PMC6458786 DOI: 10.1186/s12891-019-2510-7] [Citation(s) in RCA: 93] [Impact Index Per Article: 15.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/16/2018] [Accepted: 03/17/2019] [Indexed: 12/19/2022] Open
Abstract
We live in a world with an ever-increasing ageing population. Studying healthy ageing and reducing the socioeconomic impact of age-related diseases is a key research priority for the industrialised and developing countries, along with a better mechanistic understanding of the physiology and pathophysiology of ageing that occurs in a number of age-related musculoskeletal disorders. Arthritis and musculoskeletal disorders constitute a major cause of disability and morbidity globally and result in enormous costs for our health and social-care systems.By gaining a better understanding of healthy musculoskeletal ageing and the risk factors associated with premature ageing and senescence, we can provide better care and develop new and better-targeted therapies for common musculoskeletal disorders. This review is the outcome of a two-day multidisciplinary, international workshop sponsored by the Institute of Advanced Studies entitled "Musculoskeletal Health in the 21st Century" and held at the University of Surrey from 30th June-1st July 2015.The aim of this narrative review is to summarise current knowledge of musculoskeletal health, ageing and disease and highlight strategies for prevention and reducing the impact of common musculoskeletal diseases.
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Affiliation(s)
- Rebecca Lewis
- School of Veterinary Medicine, Faculty of Health and Medical Sciences, University of Surrey, Guildford, UK
| | - Constanza B. Gómez Álvarez
- School of Veterinary Medicine, Faculty of Health and Medical Sciences, University of Surrey, Guildford, UK
| | - Margaret Rayman
- School of Biosciences and Medicine, Faculty of Health and Medical Sciences, University of Surrey, Guildford, UK
| | - Susan Lanham-New
- School of Biosciences and Medicine, Faculty of Health and Medical Sciences, University of Surrey, Guildford, UK
| | - Anthony Woolf
- Department of Rheumatology, Royal Cornwall Hospital, Truro, UK
| | - Ali Mobasheri
- School of Veterinary Medicine, Faculty of Health and Medical Sciences, University of Surrey, Guildford, UK
- Centre for Sport, Exercise and Osteoarthritis Research Versus Arthritis, Queen’s Medical Centre, Nottingham, UK
- Department of Regenerative Medicine, State Research Institute Centre for Innovative Medicine, Vilnius, Lithuania
- The D-BOARD FP7 Consortium, http://www.d-board.eu
- The APPROACH IMI Consortium, https://www.approachproject.eu
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The Effects of Glucosamine and Chondroitin Sulfate on Gut Microbial Composition: A Systematic Review of Evidence from Animal and Human Studies. Nutrients 2019; 11:nu11020294. [PMID: 30704054 PMCID: PMC6412843 DOI: 10.3390/nu11020294] [Citation(s) in RCA: 49] [Impact Index Per Article: 8.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/04/2018] [Revised: 01/23/2019] [Accepted: 01/24/2019] [Indexed: 12/25/2022] Open
Abstract
Oral glucosamine sulfate (GS) and chondroitin sulfate (CS), while widely marketed as joint-protective supplements, have limited intestinal absorption and are predominantly utilized by gut microbiota. Hence the effects of these supplements on the gut microbiome are of great interest, and may clarify their mode of action, or explain heterogeneity in therapeutic responses. We conducted a systematic review of animal and human studies reporting the effects of GS or CS on gut microbial composition. We searched MEDLINE, EMBASE, and Scopus databases for journal articles in English from database inception until July 2018, using search terms microbiome, microflora, intestinal microbiota/flora, gut microbiota/flora and glucosamine or chondroitin. Eight original articles reported the effects of GS or CS on microbiome composition in adult humans (four articles) or animals (four articles). Studies varied significantly in design, supplementation protocols, and microbiome assessment methods. There was moderate-quality evidence for an association between CS exposure and increased abundance of genus Bacteroides in the murine and human gut, and low-quality evidence for an association between CS exposure and an increase in Desulfovibrio piger species, an increase in Bacteroidales S24-7 family, and a decrease in Lactobacillus. We discuss the possible metabolic implications of these changes for the host. For GS, evidence of effects on gut microbiome was limited to one low-quality study. This review highlights the importance of considering the potential influence of oral CS supplements on gut microbiota when evaluating their effects and safety for the host.
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Abstract
PURPOSE OF REVIEW Osteoarthritis, the most common joint disease, is associated with substantial medical costs, lost productivity, and reduced quality of life. However, available pharmaceutical treatments have limitations in terms of efficacy and long-term safety. RECENT FINDINGS In vitro evidence suggests that some natural products may possess anti-inflammatory and anti-oxidative properties and may inhibit the release of key osteoarthritis-related cytokines. There is, therefore, ongoing interest in identifying natural products that safely promote joint health and treat osteoarthritis. Numerous plant extracts, including curcumin, Boswellia extract, and pycnogenol, have shown effect sizes (ES) for reducing pain and functional disability larger than those observed with analgesics and products such as glucosamine and chondroitin. The ES for methylsulfonylmethane and avocado/soybean unsaponifiables are also considered to be clinically relevant. Data from a small number of studies using natural products for treating osteoarthritis are promising but require confirmation in further well-designed clinical trials.
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Simental-Mendía M, Sánchez-García A, Vilchez-Cavazos F, Acosta-Olivo CA, Peña-Martínez VM, Simental-Mendía LE. Effect of glucosamine and chondroitin sulfate in symptomatic knee osteoarthritis: a systematic review and meta-analysis of randomized placebo-controlled trials. Rheumatol Int 2018; 38:1413-1428. [PMID: 29947998 DOI: 10.1007/s00296-018-4077-2] [Citation(s) in RCA: 64] [Impact Index Per Article: 9.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2018] [Accepted: 06/02/2018] [Indexed: 01/10/2023]
Abstract
Although glucosamine and chondroitin sulfate have showed beneficial effects on joint tissues in osteoarthritis (OA), their therapeutic use in the clinical setting is still debatable. Hence, a systematic review and meta-analysis of randomized placebo-controlled trials was conducted to investigate the efficacy of glucosamine and chondroitin sulfate on knee OA symptoms. Medline, SCOPUS, Web of Science, and Google Scholar databases were searched for randomized placebo-controlled trials evaluating the effect of orally administered glucosamine and/or chondroitin sulfate on OA symptoms using the Western Ontario and McMaster Universities Osteoarthritis index (WOMAC) and/or the Visual Analog Scale (VAS). Meta-analysis was conducted using a random-effects model and generic inverse-variance method. Heterogeneity was tested using the I2 statistic index. Treatments with glucosamine and chondroitin were found to significantly reduce pain in VAS [weighted mean difference (WMD) - 7.41 mm, 95% CI - 14.31, - 0.51, p = 0.04 and WMD - 8.35 mm, 95% CI - 11.84, - 4.85, p < 0.00001, respectively]. Their combination did not show this behavior (WMD - 0.28 mm, 95% CI - 8.87, 8.32, p = 0.95). None of the glucosamine, chondroitin or their combination had a significant positive effect on the total WOMAC index and its subscores. Oral supplementation with glucosamine or chondroitin sulfate reduces pain in knee OA. However, there is no additional effect using both therapeutic agents in combination for the management of symptomatic knee OA.
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Affiliation(s)
- Mario Simental-Mendía
- Orthopedics and Traumatology Service, Universidad Autónoma de Nuevo León, University Hospital ''Dr. José Eleuterio González'', Monterrey, Nuevo León, Mexico
| | - Adriana Sánchez-García
- Endocrinology Division, Universidad Autónoma de Nuevo León, University Hospital ''Dr. José Eleuterio González'', Monterrey, Nuevo León, Mexico
| | - Félix Vilchez-Cavazos
- Orthopedics and Traumatology Service, Universidad Autónoma de Nuevo León, University Hospital ''Dr. José Eleuterio González'', Monterrey, Nuevo León, Mexico
| | - Carlos A Acosta-Olivo
- Orthopedics and Traumatology Service, Universidad Autónoma de Nuevo León, University Hospital ''Dr. José Eleuterio González'', Monterrey, Nuevo León, Mexico
| | - Víctor M Peña-Martínez
- Orthopedics and Traumatology Service, Universidad Autónoma de Nuevo León, University Hospital ''Dr. José Eleuterio González'', Monterrey, Nuevo León, Mexico
| | - Luis E Simental-Mendía
- Unidad de Investigación Biomédica, Delegación Durango, Instituto Mexicano del Seguro Social, Canoas 100, Col. Los Angeles, 34067, Durango, DGO, Mexico.
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Huang Z, Ding C, Li T, Yu SPC. Current status and future prospects for disease modification in osteoarthritis. Rheumatology (Oxford) 2018; 57:iv108-iv123. [PMID: 29272498 DOI: 10.1093/rheumatology/kex496] [Citation(s) in RCA: 34] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2017] [Indexed: 12/12/2022] Open
Abstract
OA is a chronic, progressive and disabling joint disease, leading to a poor quality of life and an enormous social and economic burden. Current therapies for OA patients remain limited, which creates an area of huge unmet medical need. For some time, researchers have been looking for approaches that can inhibit the structural progression of OA. A variety of potential disease-modifying OA drugs have been developed, targeting cartilage, inflammatory pathways or subchondral bone. In addition, non-pharmacological therapies, including joint distraction and weight loss, draw increasing attention, with some showing disease-modifying potential. Thus we performed a comprehensive review to discuss the current status of disease-modifying therapies in OA and appraise the potentials of emerging novel agents.
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Affiliation(s)
- Zhengping Huang
- Department of Rheumatology and Immunology, Guangdong Second Provincial General Hospital, Guangzhou, China
| | - Changhai Ding
- Department of Rheumatology and Immunology, Guangdong Second Provincial General Hospital, Guangzhou, China
- Menzies Institute for Medical Research, University of Tasmania, Hobart, Tasmania, Australia
- Translational Research Centre, Academy of Orthopedics, Guangdong Province and School of Basic Medical Sciences, Southern Medical University, Guangzhou, Guangdong, China
| | - Tianwang Li
- Department of Rheumatology and Immunology, Guangdong Second Provincial General Hospital, Guangzhou, China
| | - Shirley Pei-Chun Yu
- Department of Rheumatology, Royal North Shore Hospital and Institute of Bone and Joint Research, University of Sydney, Sydney, New South Wales, Australia
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McCarty MF, O'Keefe JH, DiNicolantonio JJ. Glucosamine for the Treatment of Osteoarthritis: The Time Has Come for Higher-Dose Trials. J Diet Suppl 2018; 16:179-192. [PMID: 29667462 DOI: 10.1080/19390211.2018.1448920] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/30/2023]
Abstract
Although clinical trials with glucosamine in osteoarthritis have yielded mixed results, leading to doubts about its efficacy, the utility of glucosamine for preventing joint destruction and inflammation is well documented in rodent models of arthritis, including models of spontaneous osteoarthritis. The benefit of oral glucosamine in adjuvant arthritis is markedly dose dependent, likely reflecting a modulation of tissue levels of UDP-N-acetylglucosamine that in turn influences mucopolysaccharide synthesis and the extent of protein O-GlcNAcylation. Importantly, the minimal oral dose of glucosamine that exerts a detectible benefit in adjuvant arthritis achieves plasma glucosamine levels similar to those achieved when the standard clinical dose of glucosamine, 1.5 g daily, is administered as a bolus. The response of plasma glucosamine levels to an increase in glucosamine intake is nearly linear. Remarkably, every published clinical trial with glucosamine has employed the same 1.5 g dose that Rottapharm recommended for its proprietary glucosamine sulfate product decades ago, yet there has never been any published evidence that this dose is optimal with respect to efficacy and side effects. If this dose is on the edge of demonstrable clinical efficacy when experimental design is ideal, then variations in the patient populations targeted, the assessment vehicles employed, and the potency of glucosamine preparations tested could be expected to yield some null results. Failure to employ bolus dosing may also be a factor in the null results observed in the GAIT study and other trials. Clinical studies evaluating the dose dependency of glucosamine's influence on osteoarthritis are long overdue.
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Affiliation(s)
| | - James H O'Keefe
- b Mid America Heart Institute , University of Missouri-Kansas City , Kansas City , MO , USA
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Vaishya R, Agarwal AK, Shah A, Vijay V, Vaish A. Current status of top 10 nutraceuticals used for Knee Osteoarthritis in India. J Clin Orthop Trauma 2018; 9:338-348. [PMID: 30449982 PMCID: PMC6224802 DOI: 10.1016/j.jcot.2018.07.015] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/11/2018] [Accepted: 07/18/2018] [Indexed: 12/11/2022] Open
Abstract
Knee Osteoarthritis (OA) is a progressive degenerative joint disease affecting the quality of life of the elderly population. There is considerable evidence that nutraceuticals from natural herbs may play a significant role in inflammation and joint destruction in OA. We review the current status of some of the commonly used nutraceuticals in Indian market - Boswellia, Aflapin, Chondroitin sulphate, Glucosamine sulphate, Collagen peptide, Curcumin, Fish Oil, Ginger, Green tea, and Rosehip extract. We have summarized their mechanism of action, biological effects, toxicities and efficacy in the management of Knee OA. These supplements have been found to be effective in knee OA in various studies. No serious side effects have been reported for any of these supplements. Overall, our study identifies and support the use of these nutraceuticals to provide symptomatic relief to patients with knee OA and justify their use as an adjunct therapy for the management. More good quality trials are needed to provide definitive answers to questions related to their efficacy and safety for OA prevention and treatment.
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Affiliation(s)
- Raju Vaishya
- Department of Orthopaedics, Indraprastha Apollo Hospital, Sarita Vihar, Mathura Road, 110076, New Delhi, India
| | - Amit Kumar Agarwal
- Department of Orthopaedics, Indraprastha Apollo Hospital, Sarita Vihar, Mathura Road, 110076, New Delhi, India,Corresponding author.
| | - Amish Shah
- Department of Orthopaedics, Indraprastha Apollo Hospital, Sarita Vihar, Mathura Road, 110076, New Delhi, India
| | - Vipul Vijay
- Department of Orthopaedics, Indraprastha Apollo Hospital, Sarita Vihar, Mathura Road, 110076, New Delhi, India
| | - Abhishek Vaish
- Department of Orthopaedics, Safdarjung Hospital, New Delhi, India
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Jeong DH, Ullah HMA, Goo MJ, Ghim SG, Hong IH, Kim AY, Jeon SM, Choi MS, Elfadl AK, Chung MJ, Lee EJ, Kim YD, Kim JH, Kim SY, Jeong KS. Effects of oral glucosamine hydrochloride and mucopolysaccharide protein in a rabbit model of osteoarthritis. Int J Rheum Dis 2017; 21:620-628. [PMID: 29205898 DOI: 10.1111/1756-185x.13239] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
AIM The aim was to study whether oral glucosamine hydrochloride (GlcN.HCl) or mucopolysaccharide protein (MucoP) has a structure-modifying effect on an anterior cruciate ligament transection (ACLT) rabbit model of osteoarthritis (OA). METHODS OA was surgically induced in the right knees of rabbits by transection of the ACLT. The left knees served as a sham-operated control. The animals were divided into four groups (n = 6 each): negative control (phosphate buffered saline, orally), positive control (oral celecoxib 10 mg/kg body weight/day), GlcN.HCl (oral 100 mg/kg/day) and MucoP (oral 100 mg/kg/day). Experimental animals were sacrificed after 8 weeks of treatment and the distal femur was removed for macroscopic examination, histological assessment, and terminal deoxynucleotidyl transferase-mediated nick-end labeling (TUNEL) assay of the OA rabbits. RESULTS On gross morphology, severe lesions were observed in articular cartilage in the negative control group. In the GlcN.HCl and MucoP treatment groups, fibrillations and cartilaginous lesions were significantly (P < 0.05) decreased compared to the negative control group. In particular, degenerative changes in cartilage and chondrocyte cellularity were significantly reduced (P < 0.05) in the positive control (celecoxib) group, GlcN.HCl treatment group and MucoP treatment group compared with the negative control group. TUNEL assay showed that apoptotic chondrocytes were significantly suppressed in the celecoxib group. Similar significant (P < 0.05) results were seen in the GlcN.HCl group and MucoP group but apoptosis of chondrocytes were high in the negative control group. CONCLUSION These data suggest that the protective effects of GlcN.HCl and MucoP may play a useful role in the clinical treatment of OA.
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Affiliation(s)
- Da-Hee Jeong
- Department of Pathology, Kyungpook National University, Daegu, Korea
| | - H M Arif Ullah
- Department of Pathology, Kyungpook National University, Daegu, Korea
| | - Moon-Jung Goo
- Department of Pathology, Kyungpook National University, Daegu, Korea
| | - Soong-Gu Ghim
- Department of Pathology, Kyungpook National University, Daegu, Korea
| | - Il-Hwa Hong
- Department of Pathology, Kyungpook National University, Daegu, Korea
| | - Ah-Young Kim
- Department of Pathology, Kyungpook National University, Daegu, Korea
| | - Sun-Min Jeon
- Department of Food Science and Nutrition, Kyungpook National University, Daegu, Korea
| | - Myung-Sook Choi
- Department of Food Science and Nutrition, Kyungpook National University, Daegu, Korea
| | - Ahmed K Elfadl
- Department of Pathology, Kyungpook National University, Daegu, Korea
| | - Myung-Jin Chung
- Department of Pathology, Kyungpook National University, Daegu, Korea
| | - Eun-Joo Lee
- Department of Pathology, Kyungpook National University, Daegu, Korea
| | - Yong D Kim
- Department of Pathology, Kyungpook National University, Daegu, Korea
| | - Jun-Hyung Kim
- Department of Orthopedic Surgery, Kyungpook National University, Daegu, Korea
| | - Shin-Yoon Kim
- Department of Orthopedic Surgery, Kyungpook National University, Daegu, Korea
| | - Kyu-Shik Jeong
- Department of Pathology, Kyungpook National University, Daegu, Korea
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Feng X, Beiping L. Therapeutic Efficacy of Ozone Injection into the Knee for the Osteoarthritis Patient along with Oral Celecoxib and Glucosamine. J Clin Diagn Res 2017; 11:UC01-UC03. [PMID: 29207809 DOI: 10.7860/jcdr/2017/26065.10533] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2016] [Accepted: 06/26/2017] [Indexed: 01/12/2023]
Abstract
Introduction Suffering from osteoarthritis is prevalent among elderly patients so the use of intra-articular injection of medical ozone may well be the effective way to relieve their pain. Aim To evaluate the effect of intra-articular injection of medical ozone given into the knee of the osteoarthritis patients, and to compare it with taking celecoxib and glucosamine orally. Materials and Methods In the present study, 76 patients suffering from osteoarthritis were randomly assigned into two groups. In the ozone group, 20 ml ozone-oxygen mixture gas concentration of 20 μg/ml was injected into knee articular cavity and each patient took oral celecoxib and glucosamine hydrochloride. Patients in control group only took the celecoxib and glucosamine hydrochloride orally.Pain score and Lysholm knee score were measured prior to the injection (pretreatment) and at one, three, six weeks after the beginning of the treatment (posttreatment). Results After the treatment, the pain intensity and function significantly improved in the two groups compared with the pretreatment (p<0.05). In the ozone group, three weeks after intervention, the pain score improved significantly when compared with the control group (p<0.05).After the treatment, the lysholm scores increased significantly (p<0.05), but in the ozone group, it improved faster. Conclusion Intra-articular injection of ozone plus oral celecoxib and glucosamine could significantly decrease pain intensity in patients with mild to moderate Knee Osteoarthritis (KOA), and improve their functional status early than oral celecoxib and glucosamine only.
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Affiliation(s)
- Xu Feng
- Associate Professor, Department of Anaesthesiology, Xuzhou First People's Hospital, Xuzhou, Jiangsu, China
| | - Li Beiping
- Chief Physician, Department of Anaesthesiology, Xuzhou First People's Hospital, Xuzhou, Jiangsu, China
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Yao H, Xue J, Wang Q, Xie R, Li W, Liu S, Cai J, Qin D, Wang DA, Ren L. Glucosamine-modified polyethylene glycol hydrogel-mediated chondrogenic differentiation of human mesenchymal stem cells. MATERIALS SCIENCE & ENGINEERING. C, MATERIALS FOR BIOLOGICAL APPLICATIONS 2017. [PMID: 28629066 DOI: 10.1016/j.msec.2017.05.043] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Glucosamine (GA) is an important cartilage matrix precursor for the glycosaminoglycan biochemical synthesis, and has positive effects on cartilage regeneration, particularly in osteoarthritis therapy. However, it has not been used as a bioactive group in scaffolds for cartilage repair widely. In this study, we synthesized modified polyethylene glycol (PEG) hydrogel with glucosamine and then encapsulated human bone mesenchymal stem cells (hBMSCs) in the hydrogel to induce the differentiation of hBMSCs into chondrocytes in three-dimensional culture. The GA-modified PEG hydrogels promoted the chondrogenesis of hBMSCs, particularly in the concentration of 5mM and 10mM. The subcutaneous transplantation of 10mM GA-modified hydrogels with hBMSCs formed cartilage-like blocks in vivo for 8weeks. Importantly, with glucosamine increase, the modified hydrogels down-regulated the fibrosis and hypertrophic cartilage markers in protein level. Therefore, glucosamine modified PEG hydrogels facilitated the chondrogenesis of hBMSCs, which might represent a new method for cartilage repair using a tissue-engineering approach.
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Affiliation(s)
- Hang Yao
- School of Materials Science and Engineering, South China University of Technology, Wushan RD, Tianhe District, Guangzhou 510641, China; National Engineering Research Center for Tissue Restoration and Reconstruction, Guangzhou 510006, China; Key Laboratory of Regenerative Biology, Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, South China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, China; Division of Bioengineering, School of Chemical & Biomedical Engineering, Nanyang Technological University, 70 Nanyang Drive, N1.3-B2-13, 637457, Singapore
| | - Jingchen Xue
- School of Materials Science and Engineering, South China University of Technology, Wushan RD, Tianhe District, Guangzhou 510641, China; National Engineering Research Center for Tissue Restoration and Reconstruction, Guangzhou 510006, China
| | - Qunfang Wang
- School of Materials Science and Engineering, South China University of Technology, Wushan RD, Tianhe District, Guangzhou 510641, China; National Engineering Research Center for Tissue Restoration and Reconstruction, Guangzhou 510006, China
| | - Renjian Xie
- School of Materials Science and Engineering, South China University of Technology, Wushan RD, Tianhe District, Guangzhou 510641, China; National Engineering Research Center for Tissue Restoration and Reconstruction, Guangzhou 510006, China
| | - Weichang Li
- School of Materials Science and Engineering, South China University of Technology, Wushan RD, Tianhe District, Guangzhou 510641, China
| | - Sa Liu
- School of Materials Science and Engineering, South China University of Technology, Wushan RD, Tianhe District, Guangzhou 510641, China; National Engineering Research Center for Tissue Restoration and Reconstruction, Guangzhou 510006, China
| | - Jinglei Cai
- Key Laboratory of Regenerative Biology, Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, South China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, China
| | - Dajiang Qin
- Key Laboratory of Regenerative Biology, Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, South China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, China.
| | - Dong-An Wang
- Division of Bioengineering, School of Chemical & Biomedical Engineering, Nanyang Technological University, 70 Nanyang Drive, N1.3-B2-13, 637457, Singapore.
| | - Li Ren
- School of Materials Science and Engineering, South China University of Technology, Wushan RD, Tianhe District, Guangzhou 510641, China; National Engineering Research Center for Tissue Restoration and Reconstruction, Guangzhou 510006, China.
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Nutraceutical/Alternative Remedies in the Management of OA. CURRENT TREATMENT OPTIONS IN RHEUMATOLOGY 2017. [DOI: 10.1007/s40674-017-0064-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/19/2022]
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Santos GRC, Piquet AA, Glauser BF, Tovar AMF, Pereira MS, Vilanova E, Mourão PAS. Systematic Analysis of Pharmaceutical Preparations of Chondroitin Sulfate Combined with Glucosamine. Pharmaceuticals (Basel) 2017; 10:E38. [PMID: 28368296 PMCID: PMC5490395 DOI: 10.3390/ph10020038] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/26/2017] [Revised: 03/28/2017] [Accepted: 03/30/2017] [Indexed: 11/24/2022] Open
Abstract
Glycosaminoglycans are carbohydrate-based compounds widely employed as nutraceuticals or prescribed drugs. Oral formulations of chondroitin sulfate combined with glucosamine sulfate have been increasingly used to treat the symptoms of osteoarthritis and osteoarthrosis. The chondroitin sulfate of these combinations can be obtained from shark or bovine cartilages and hence presents differences regarding the proportions of 4- and 6-sulfated N-acetyl β-d-galactosamine units. Herein, we proposed a systematic protocol to assess pharmaceutical batches of this combination drug. Chemical analyses on the amounts of chondroitin sulfate and glucosamine in the batches were in accordance with those declared by the manufacturers. Anion-exchange chromatography has proven more effective than electrophoresis to determine the type of chondroitin sulfate present in the combinations and to detect the presence of keratan sulfate, a common contaminant found in batches prepared with shark chondroitin sulfate. 1D NMR spectra revealed the presence of non-sulfated instead of sulfated glucosamine in the formulations and thus in disagreement with the claims declared on the label. Moreover, 1D and 2D NMR analyses allowed a precise determination on the chemical structures of the chondroitin sulfate present in the formulations. The set of analytical tools suggested here could be useful as guidelines to improve the quality of this medication.
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Affiliation(s)
- Gustavo R C Santos
- Laboratório de Tecido Conjuntivo, Hospital Universitário Clementino Fraga Filho and Instituto de Bioquímica Médica Leopoldo de Meis, Universidade Federal do Rio de Janeiro (UFRJ), P.O. Box 68041, Rio de Janeiro RJ 21941-913, Brazil.
| | - Adriana A Piquet
- Laboratório de Tecido Conjuntivo, Hospital Universitário Clementino Fraga Filho and Instituto de Bioquímica Médica Leopoldo de Meis, Universidade Federal do Rio de Janeiro (UFRJ), P.O. Box 68041, Rio de Janeiro RJ 21941-913, Brazil.
| | - Bianca F Glauser
- Laboratório de Tecido Conjuntivo, Hospital Universitário Clementino Fraga Filho and Instituto de Bioquímica Médica Leopoldo de Meis, Universidade Federal do Rio de Janeiro (UFRJ), P.O. Box 68041, Rio de Janeiro RJ 21941-913, Brazil.
| | - Ana M F Tovar
- Laboratório de Tecido Conjuntivo, Hospital Universitário Clementino Fraga Filho and Instituto de Bioquímica Médica Leopoldo de Meis, Universidade Federal do Rio de Janeiro (UFRJ), P.O. Box 68041, Rio de Janeiro RJ 21941-913, Brazil.
| | - Mariana S Pereira
- Laboratório de Tecido Conjuntivo, Hospital Universitário Clementino Fraga Filho and Instituto de Bioquímica Médica Leopoldo de Meis, Universidade Federal do Rio de Janeiro (UFRJ), P.O. Box 68041, Rio de Janeiro RJ 21941-913, Brazil.
| | - Eduardo Vilanova
- Laboratório de Tecido Conjuntivo, Hospital Universitário Clementino Fraga Filho and Instituto de Bioquímica Médica Leopoldo de Meis, Universidade Federal do Rio de Janeiro (UFRJ), P.O. Box 68041, Rio de Janeiro RJ 21941-913, Brazil.
| | - Paulo A S Mourão
- Laboratório de Tecido Conjuntivo, Hospital Universitário Clementino Fraga Filho and Instituto de Bioquímica Médica Leopoldo de Meis, Universidade Federal do Rio de Janeiro (UFRJ), P.O. Box 68041, Rio de Janeiro RJ 21941-913, Brazil.
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Wenz W, Hornung C, Cramer C, Schroeder M, Hoffmann M. Effect of Glucosamine Sulfate on Osteoarthritis in the Cruciate-Deficient Canine Model of Osteoarthritis. Cartilage 2017; 8:173-179. [PMID: 28345412 PMCID: PMC5358821 DOI: 10.1177/1947603516638898] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Objective Osteoarthritis (OA) is a major cause of musculoskeletal pain and disability worldwide. The investigation of disease-modifying treatment options for OA has become an important aspect of orthopedic care. To assess the effect of intra-articular and oral glucosamine sulfate (GS) versus placebo on osteoarthritis in a canine model. Materials In this randomized, placebo-controlled, double-blinded study, OA was induced by anterior cruciate ligament transection (ACLT) according to the Pond-Nuki model in 32 canines. All canines were allocated into 4 treatment subgroups with treatment administered for 8 weeks: GS (400 mg) intra-articular, placebo intra-articular, GS (200 mg/kg body weight) oral, and placebo oral. The contralateral nonoperated stifle (knee) served as control. After 8 weeks, the medial and lateral femoral condyles, the medial and lateral tibial plateau and patella were histologically examined and anatomic changes quantified by light microscopy using the modified Mankin score. Results After 8 weeks, mean Mankin score values significantly ( P < 0.002) decreased in the intra-articular GS group (8.1; range 7.9-8.8) compared with the intra-articular placebo group (13.9; range 11.6-15.9) and again significantly ( P < 0.002) in the oral GS group (12.1; range 9.9-12.7) compared with the oral placebo group (15.1; range 12.5-17.0). Mean Mankin score values were significantly ( P < 0.002) lower in the intra-articular GS group compared with the oral GS group. Conclusion Both, intra-articular and oral administered GS significantly reduced histological signs of OA in the Pond-Nuki model, with the intra-articular application being more effective compared to oral administration.
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Affiliation(s)
| | | | - Christopher Cramer
- Department of Trauma, Hand and Reconstructive Surgery, University Medical Centre, Hamburg-Eppendorf, Hamburg, Germany
| | - Malte Schroeder
- Department of Trauma, Hand and Reconstructive Surgery, University Medical Centre, Hamburg-Eppendorf, Hamburg, Germany
| | - Michael Hoffmann
- Department of Trauma, Hand and Reconstructive Surgery, University Medical Centre, Hamburg-Eppendorf, Hamburg, Germany,Michael Hoffmann, Department of Trauma, Hand and Reconstructive Surgery, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, D-20246 Hamburg, Germany.
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