Influence of hypoxia on the expression of matrix metalloproteinase-1, -3 and tissue inhibitor of metalloproteinase-1 in rheumatoid synovial fibroblasts.
OBJECTIVE
The rheumatoid synovium is a hypoxic environment, and hypoxia has been implicated as a factor in the pathogenesis of rheumatoid arthritis (RA). The purpose of this study was to investigate the effect of hypoxia on the expression of matrix metalloproteinase (MMP)-1, -3 and tissue inhibitor of metalloproteinase (TIMP)-1 in rheumatoid synovial fibroblasts.


METHODS
Synovial fibroblasts obtained from RA patients were cultured for 48 h under normoxic or hypoxic conditions. Assays included western blot analysis and enzyme-linked immunosorbent assay (ELISA) for MMP-1, -3 and TIMP-1, and northern blot analysis to measure TIMP-1 mRNA levels.


RESULTS
Compared with normoxic culture, hypoxia increased MMP-1 and MMP-3 expression in rheumatoid synovial fibroblasts. Hypoxia decreased TIMP-1 expression in rheumatoid synovial fibroblasts, as measured by both protein and mRNA levels.


CONCLUSIONS
These results suggest that microenvironmental conditions, such as hypoxia, may directly contribute to joint destruction in RA by increasing the ratio of MMP-1, -3 to TIMP-1 production in synovial fibroblasts.
Cha
H S
HS
Department of Medicine, Samsung Medical Center, Seoul, Korea. chahs@samsung.co.kr
Ahn
K S
KS
Jeon
C H
CH
Kim
J
J
Song
Y W
YW
Koh
E M
EM
D001172:Arthritis, Rheumatoid / Q000201:enzymology*; D015152:Blotting, Northern; D015687:Cell Hypoxia; D002478:Cells, Cultured; D004797:Enzyme-Linked Immunosorbent Assay; D005347:Fibroblasts / Q000378:metabolism*; D006801:Humans; D020781:Matrix Metalloproteinase 1 / Q000032:analysis*; D019278:Matrix Metalloproteinase 3 / Q000032:analysis*; D013583:Synovial Membrane / Q000378:metabolism*; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000032:analysis*
D019715:Tissue Inhibitor of Metalloproteinase-1; D019278:Matrix Metalloproteinase 3; D020781:Matrix Metalloproteinase 1