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OP0025 Glucosamine Sulfate Inhibits Nitric Oxide and Stromelysin Production in Cartilage Cultures and Reverses IL-1 Inhibition of Osteoarthritic Articular Cartilage Synthesis I Yaron, I Shirazi, R Judovich, M Yaron The primary enzymes responsible for the degradation of cartilage are the matrix metalloproteinases (MMPs). Under normal conditions, MMP synthesis, activation, and inhibition are tightly regulated at several levels. In OA, synthesis of MMPs is greatly enhanced, overwhelming the available inhibitors. Nitric oxide has been implicated as a possible mediator of osteoarthritis development and cartilage deterioration. (read more about the pathophysiology of OA) The purpose of this study was to elucidate the mechanism by which Glucosamine sulfate plays a role in managing OA in the knee. Cartilage from OA patients undergoing total knee replacement was cultured with and without IL-1b(1 ng/ml) or LPS (3 g/ml) in the presence of Glucosamine sulfate (1, 10, and 100 g/ml). Nitrous oxide (NO) and stromelysis (MMP-3) content in the culture media, as well as cartilage synthesis by 35S incorporation were measured. There was a four-fold increase in nitrous oxide release present in both IL-1band LPS cultures that was inhibited in a dose-dependent manner by Glucosamine sulfate, reaching statistical significance at a dose of 100 g/ml, 60% and 38% (P<0.05), respectively. IL-1band LPS stimulated MMP-3 production was also significantly (P<0.05) inhibited by Glucosamine sulfate at a dose of 100 g/ml. The inhibition of cartilage synthesis by IL-1b(70%) and LPS (50%) cultures was reversed by the presence of Glucosamine sulfate, reaching statistical significance (P<0.05) at 10 g/ml. Glucosamine sulfate may minimize the damage to articulate cartilage in patients with OA by blocking the inhibition of cartilage synthesis by IL-1band by inhibiting NO and MMP-3 production. Editorial Comment: There is increasing evidence that glucosamine (GC) may inhibit cartilage degradation and thus be disease modifying in OA. This abstract presents a possible mechanism. In vitro studies are always subject to criticism because effects may not mirror those in intact tissue. In addition, there needs to be an assessment of whether the doses of GC used in the in vitro study are physiologically obtainable in the joint. However, the information is intriguing and deserves further study. | ||||||
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OP0052 Glucosamine Sulfate as an Osteoarthritis Disease Modification Agent: A Confirmatory Long-Term, Randomized, Placebo-Controlled Independent Study K. Pavelka, J. Gatterova, M. Olejarova, S. Machacek, C. Gonzalez, G. Giacovelli, L.C. Rovati Methods: 202 patients with knee osteoarthritis (OA) were randomized to receive glucosamine sulfate (GC) 1500 mg daily or palcebo for three years. Primary outcome at three years was minimum joint space width (JSW) at narrowest medial compartment of the tibiofemoral joint on standardized weight bearing radiographs at full extension. Results: Intent to treat analysis
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| Change JSW | +0.02 mm (0.05)** | |||||
Pains scores measured by the WOMAC, also improved significantly in the GC treated group.
Editorial Comment: These results, as the authors have acknowledged, are similar to those already published by another group (Lancet 2001;357:251-256). However there is clear benefit to have confirmatory study. Although criticism can be made about the use of extended weight bearing radiographic views of the knees versus the more accepted semi-flexed views, the results are significant. This study can be added to the mounting evidence that GC has disease modifying activity in OA.
