The Expression Of MMP-12 In RA And OA And The Treatment Of Chinese Medicine On RA.

OBJECTIVE: Extracellular matrix (ECM) synthesis and breakdown is mediated by the matrix metalloproteinases (MMPs). Human metallolastase (MMP-12) is a MMP, the abnormal expression of which has so far been documented in macrophages associated with many diseases, such as rheumatoid arthritis (RA) and osteoarthritis (OA).The aim of this study was to explore synovial membrane and fluid expression of MMP-12 in RA and OA,and to examine the effect of Chinese medicine on RA. METHODS: We obtained synovial tissues from 22 RA and 29 OA patients and analyzed MMP-12 expression using immunohistochemistry, Western and Northern blot analysis, and zymography. Furthermore, we quantified in the synovial fluid by Western blot and zymography ,at the same time ,we compared the MMP-12 levels in the synovial tissue of Chinese medicine group with no Chinese medicine group by Northern blot analysis .RESULTS: Northern blot analysis demonstrated that RA synovial tissue contained higher levels of MMP-12 mRNA than did OA synovial tissue. Western blot revealed that MMP-12 proteins were consistently and markedly increased patients. A greater amount of immunoreactive proteins corresponding to catalytic forms of MMP-12 was present in RA synovial tissue and fluids. The total amounts of catalytic MMP-12 proteins (OA)recovered from RA tissue and synovial fluid were 6.5-fold and 10-fold, respectively, greater than those from OA, and the extracted enzymes exhibited activity in vitro. Immunohistochemical staining showed that the major cells that expressed MMP-12 were synovial lining cells, many of which were inflammatory macrophages. Importantly, increased MMP-12 expression in RA was also associated with high expression of MMP-3. Chinese medicine only reduced MMP-12 expression in Western blot slightly. CONCLUSION: These results establish a possible mechanism by which macrophage-derived MMP-12 may play an important role in the destructive process of RA. Chinese medicine may be a potential therapeutic modality for the treatment of RA patients.