Regulation of Matrix Metalloproteinases and Tissue Inhibitor of Metalloproteinase-1 Expression by Hypoxia in Rheumatoid and Osteoarthritis Fibroblast-Like Synoviocytes.
- Author:
Hoon Suk CHA
1
;
Chan Hong JEON
;
Hwa Jung CHOI
;
Kwang Sung AHN
;
Yeong Wook SONG
;
Eun Mi KOH
Author Information
1. Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
- Publication Type:Original Article
- Keywords:
Hypoxia;
Rheumatoid arthritis;
Matrix metalloproteinase;
Tissue inhibitor of metalloproteinase
- MeSH:
Anoxia*;
Arthritis, Rheumatoid;
Blotting, Northern;
Blotting, Western;
Hand;
Humans;
Joints;
Matrix Metalloproteinases*;
Osteoarthritis*;
RNA, Messenger;
Synovial Membrane;
Tissue Inhibitor of Metalloproteinase-1*
- From:The Journal of the Korean Rheumatism Association
2003;10(2):141-150
- CountryRepublic of Korea
- Language:Korean
-
Abstract:
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.
