Teriparatide prevented synovial inflammation and cartilage destruction in mice with DMM

AimEmerging data have demonstrated that low-grade inflammation in osteoarthritis, a long-held degenerative disease. The inflamed synovium produces various cytokines that induce cartilage destruction and joint pain. A previous study showed that teriparatide, an FDA approved anti-osteoporotic drug, may enhance cartilage repair. Our study focuses on its role in OA synovitis.Materials and MethodsPrimary mouse articular chondrocytes were used to determine the most potent cytokines involved in OA inflammation and cartilage destruction. A destabilization of the medial meniscus mouse model was established to investigate the effect of teriparatide in OA, particularly, on synovial inflammation and cartilage degradation.ResultsIn vitro experiments showed that TNF-alpha was the most potent inducer of cartilage matrix-degrading enzymes, and that teriparatide antagonized the TNF-alpha of effect. Consistently, articular cartilage samples from TNF-alpha transgenic mice contained more MMP-13 positive chondrocytes than those from wild type mice. In addition, more type II collagen was cleaved in human OA cartilage than in normal cartilage samples.ConclusionsTeriparatide can prevent synovitis and cartilage degradation by suppressing TNF-alpha mediated MMP-13 overexpression. Together with its chondroregenerative capability, teriparatide may be the first effective disease modifying osteoarthritis drug.