류마티스 및 골관절염 섬유모세포양 활막세포에서 저산소증에 의한 Matrix Metalloproteinase 및 Tissue Inhibitor of Metalloproteinase-1 발현의 조절

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.