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. CONCLUSION: 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.
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 RApatients 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. CONCLUSION: 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.
Authors: Mohammed A Akhavani; Leigh Madden; Ian Buysschaert; Branavan Sivakumar; Norbert Kang; Ewa M Paleolog Journal: Arthritis Res Ther Date: 2009-05-08 Impact factor: 5.156
Authors: Simona Simmen; Max Maane; Sarah Rogler; Katherina Baebler; Silvia Lang; Jesus Cosin-Roger; Kirstin Atrott; Isabelle Frey-Wagner; Partick Spielmann; Roland H Wenger; Bruce Weder; Jonas Zeitz; Stephan R Vavricka; Gerhard Rogler; Cheryl de Vallière; Martin Hausmann; Pedro A Ruiz Journal: Inflamm Intest Dis Date: 2021-03-29
Authors: Chenqi Zhao; Uriel Moreno-Nieves; John A Di Battista; Maria J Fernandes; Mohamed Touaibia; Sylvain G Bourgoin Journal: Mediators Inflamm Date: 2015-10-18 Impact factor: 4.711