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J Korean Rheum Assoc. 2003 Jun;10(2):141-150. Korean. Original Article.
Cha HS , Jeon CH , Choi HJ , Ahn KS , Song YW , Koh EM .
Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Seoul, Korea.
Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea.

OBJECTIVE: The rheumatoid synovium is a hypoxic environment and hypoxia has been implicated to have a role in the pathogenesis of rheumatoid arthritis (RA). In this work, we tried to investigate the effect of hypoxia on the expression of matrix metalloproteinase (MMP)-1, -3 and tissue inhibitor of metalloproteinase (TIMP)-1 in rheumatoid and osteoarthritis (OA) fibroblast-like synoviocytes (FLS). METHODS: FLS obtained from RA and OA patients were cultured under normoxic or hypoxic condition for 48 hours. Western blot analyses for MMP-1, -3 and TIMP-1 were performed. TIMP-1 mRNA levels were measured by Northern blot analysis. RESULTS: Hypoxia increased MMP-1 expression in rheumatoid FLS compared with normoxia. TIMP-1 expression was decreased by hypoxia in rheumatoid FLS in both protein and mRNA levels. On the other hand, hypoxia did not significantly affect MMP-1, -3 and TIMP-1 expressions in OA FLS. CONCLUSION: These results suggest that microenvironment such as hypoxia may directly contribute to joint destruction in RA by increasing the ratio of MMP-1 to TIMP-1 production in FLS.

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