Study on matrix metalloproteinase activities and cartilage degradation of the temporomandibular joint

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We have shown that several types of matrix metalloproteinases MMPs with different substrate specificities were detectable in synovial fluid(SF) from patients who suffered from temporomandibular disorders(TMD). Among these MMPs, existence of MMP-1,2,3, and 9 were correlated to bone morphologic changes of the TMJ. Our deta have also shown that induction of the active-form of MMP9 and MMP3 was important for cartilage degradation in TMJ with internal derangement(ID), which further proceeds to osteoarthritis. To further test the hypothesis that TMJ chondrocytes and disc cells synthesize specific MMPs in vitro upon cytokine stimulation, we isolated these cells from IL-1-injected rat TMJs. MMP9 and MMP3 syntheses were inducible in these cells by IL-1, whereas MMP2 was constitutively expressed on both cell types. Our studies also demonstrated that pro-forms of MMP9 and MMP3 were converted into their active-forms in vitro by IL-1 stimulation, whereas IL-1 had no remarkable effect on expression of inhibitors of MMPs(TIMPs). These results indicate that MMP9 and MMP3 are predominantly produced by disc cells and chondrocytes, and the activation of the MMPs may be regulated by proinflammatory cytokines(IL-1 and/or TNFα). These findings also suggest that IL-1 or TNFα, which usually exists in SF of patients with ID or OA, may have important roles in synthesis and activation of ECM-degrading proteinases, thereby exacerbating cartilage breakdown.