Effect of glucosamine and chondroitin sulfate on regulation of gene expression of proteolytic enzymes and their inhibitors in interleukin-1–challenged bovine articular cartilage explants

Chan, Pooi-See; Caron, John P.; Orth, Michael

doi:10.2460/ajvr.2005.66.1870

Cited by 85 publications

(77 citation statements)

References 55 publications

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“…MMPs, aggrecanases, and their post-translational activation mechanisms are obvious targets for clinical intervention in arthritis, and many natural and synthetic inhibitors have been investigated for potential therapeutic use (Chan, et al, 2005;Close, 2001). Indeed, a broad spectrum metalloproteinase inhibitor was found to reduce aggrecan depletion and loss of material properties in IL-1-stimulated cartilage explants .…”

Section: Introductionmentioning

confidence: 99%

Selective and non-selective metalloproteinase inhibitors reduce IL-1-induced cartilage degradation and loss of mechanical properties

et al. 2007

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Articular cartilage undergoes matrix degradation and loss of mechanical properties when stimulated with proinflammatory cytokines such as interleukin-1 (IL-1). Aggrecanases and matrix metalloproteinases (MMPs) are thought to be principal downstream effectors of cytokine-induced matrix catabolism, and aggrecanase-or MMP-selective inhibitors reduce or block matrix destruction in several model systems. The objective of this study was to use metalloproteinase inhibitors to perturb IL-1-induced matrix catabolism in bovine cartilage explants and examine their effects on changes in tissue compression and shear properties. Explanted tissue was stimulated with IL-1 for up to 24 days in the absence or presence of inhibitors which were aggrecanase-selective, MMP-selective, or non-selective. Analysis of conditioned media and explant digests revealed that aggrecanase-mediated aggrecanolysis was delayed to varying extents with all inhibitor treatments, but that aggrecan release persisted. Collagen degradation was abrogated by MMP-and non-selective inhibitors and reduced by the aggrecanase inhibitor. The inhibitors delayed but did not reduce loss of the equilibrium compression modulus, whereas the loss of dynamic compression and shear moduli was delayed and reduced. The data suggest that non-metalloproteinase mechanisms participate in IL-1-induced matrix degradation and loss of tissue material properties.

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Section: Introductionmentioning

confidence: 99%

Selective and non-selective metalloproteinase inhibitors reduce IL-1-induced cartilage degradation and loss of mechanical properties

et al. 2007

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“…More interestingly, there are also very few studies that describe the efficacy of a drug combination (i.e., GS-CS) in improving cartilage repair processes (Chan et al, 2005). The findings of our study appear to complement previous clinical studies in animals and in vitro conditions, demonstrating that: (1) combined therapy has been shown to have protective and beneficial effects in vitro by acting synergistically in stimulating the production of PGs in articular cartilage, while inhibiting the activity of the degradative enzymes (Dechant et al, 2005), and (2) in studies involving animal models, this combination is shown to exert a protective effect on cartilage degradation (Bassleer et al, 1998;Chan et al, 2005). However, these findings are not consistently supported by others, with many reports showing mixed results (Lipeela et al, 2000;Orth et al, 2002;Dodge and Jimenez, 2003;Ilic et al, 2003;Lippiello, 2003;Persiani et al, 2004).…”

Section: T Kamarul Et Al Surgically Treated and Untreated Focal Cartmentioning

confidence: 99%

A preliminary study of the effects of glucosamine sulphate and chondroitin sulphate on surgically treated and untreated focal cartilage damage

Kamarul¹,

Ab‐Rahim²,

Tumin³

et al. 2011

eCM

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The effects of Glucosamine Sulphate (GS) and Chondroitin Sulphate (CS) on the healing of damaged and repaired articular cartilage were investigated. This study was conducted using 18 New Zealand white rabbits as experimental models. Focal cartilage defects, surgically created in the medial femoral condyle, were either treated by means of autologous chondrocyte implantation (ACI) or left untreated as controls. Rabbits were then divided into groups which received either GS+/-CS or no pharmacotherapy. Three rabbits from each group were sacrificed at 12 and 24 weeks post-surgery. Knees dissected from rabbits were then evaluated using gross quantification of repair tissue, glycosaminoglycan (GAG) assays, immunoassays and histological assessments. It was observed that, in contrast to untreated sites, surfaces of the ACI-repaired sites appeared smooth and continuous with the surrounding native cartilage. Histological examination demonstrated a typical hyaline cartilage structure; with proteoglycans, type II collagen and GAGs being highly expressed in repair areas. The improved regeneration of these repair sites was also noted to be significant over time (6 months vs. 3 months) and in GS and GS+CS groups compared to the untreated (without pharmacotherapy) group. Combination of ACI and pharmacotherapy (with glucosamine sulphate alone/ or with chondroitin sulphate) may prove beneficial for healing of damaged cartilage, particularly in relation to focal cartilage defects.

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“…In joint tissues affected by OA, CS has been shown to modify the chondrocyte death process 17,18) and promote subchondral bone homeostasis, 19) partly by reducing some proinflammatory and catabolic factors, such as nuclear-factor κB, and increasing anabolic factors. [20][21][22] The study by Morreale et al shows that oral CS needs to be administered for longer than diclofenac to produce a substantial reduction in the pain of knee OA, but that the effects of CS persist beyond treatment. 23) Given that repeated treatment is needed for benefits to appear with oral CS therapy in OA, it is considered a slow-acting drug.…”

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confidence: 99%

Efficacy of Chondroitin Sulfate for Painful Knee Osteoarthritis: A One-Year, Randomized, Double-Blind, Multicenter Clinical Study in Japan

Morita

Yamada

Date

et al. 2018

Biological & Pharmaceutical Bulletin

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We explored the effects of chondroitin sulfate on knee osteoarthritis in a one-year, randomized, doubleblind, dose-comparison study. Patients with painful, Kellgren-Lawrence grade 2-3, osteoarthritis of the knee were treated with oral chondroitin sulfate at a dose of either 260 mg/d (low-dose group, control group) or 1560 mg/d (high-dose group). Symptoms were evaluated by the Lequesne's index and visual analog scale for pain. We made subgroup analyses according to background symptom severity (Lequesne's index ≥8 or <8) in 73 patients. Serum level of cartilage oligomeric matrix protein and hyaluronic acid were also determined. In the subgroup with severe symptoms (Lequesne's index ≥8), the chondroitin sulfate dose of 1560 mg/d improved pain faster after 6 and 9 months' therapy. However, no dose-related effects were found on cartilage oligomeric matrix protein or hyaluronic acid levels. Chondroitin sulfate also had good tolerability. We conclude that chondroitin sulfate is useful for pain control in knee osteoarthritis.Key words chondroitin sulfate; pain-management; clinical trial; randomized controlled trial Osteoarthritis (OA) is the most common form of arthritis and is a major cause of morbidity, activity limitation, physical disability, excess health care utilization, and reduced healthrelated QOL, especially in people aged 65 years and older.

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Effect of glucosamine and chondroitin sulfate on regulation of gene expression of proteolytic enzymes and their inhibitors in interleukin-1–challenged bovine articular cartilage explants

Cited by 85 publications

References 55 publications

Selective and non-selective metalloproteinase inhibitors reduce IL-1-induced cartilage degradation and loss of mechanical properties

Selective and non-selective metalloproteinase inhibitors reduce IL-1-induced cartilage degradation and loss of mechanical properties

A preliminary study of the effects of glucosamine sulphate and chondroitin sulphate on surgically treated and untreated focal cartilage damage

Efficacy of Chondroitin Sulfate for Painful Knee Osteoarthritis: A One-Year, Randomized, Double-Blind, Multicenter Clinical Study in Japan

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