Journal
CONNECTIVE TISSUE RESEARCH
Volume 52, Issue 3, Pages 190-197Publisher
INFORMA HEALTHCARE
DOI: 10.3109/03008207.2010.508853
Keywords
rheumatoid arthritis; fibroblast-like synoviocytes; matrix metalloproteinase; prostaglandin E2; cyclooxygenase-2; NF-kappa B; I kappa B-alpha; I kappa B-beta
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Funding
- National Basic Research Program of China [2005CB522703]
- Innovation and Attracting Talents Program for College and University (111 Project) [B06023]
- National Natural Science Foundation of China (NSFC) [30870608]
- CQ CSTC (CSTC) [2009AA5045]
- Chongqing University's Large-Scale Equipment
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In rheumatoid arthritis (RA), fibroblast-like synoviocytes (FLS) are one of the primary sources of inflammatory cytokines, including prostaglandins (PGs) and matrix metalloproteinases (MMPs) in joints that are detrimental to the bone, cartilage, and the surrounding tissue. Many studies, in recent years, have shown that physiotherapies play a beneficial effect on the maintenance of joint homeostasis in RA; however, the underlying mechanisms involved are still not fully elucidated. This study was performed to investigate cellular mechanism of mechanical strain-mediated actions in RA-FLS. RA-FLS were grown on collagen-coated silicone membranes and were exposed to 6% cyclic mechanical stretch at a frequency of 0.5 Hz for different times in the presence/absence of IL-1 beta. Real-time PCR and western blotting were used to detect the mRNA and protein level of cyclooxygenase-2 (COX-2) and MMP-1. The production of prostaglandin E-2 (PGE(2)) was quantified by ELISA method. Our results showed that 6% cyclic mechanical stretch significantly inhibited IL-1 beta-induced MMP-1 (gene) and COX-2 (gene and protein) expression at 15, 40, and 80 min. It also downregulated the IL-1 beta-induced production of PGE(2). Further investigation of nuclear factor kappa B (NF-kappa B) signal pathway-related effectors I kappa B-alpha and I kappa B-beta revealed that 6% cyclic stretch inhibited their IL-1 beta-induced degradation in cytoplasm as well as reversed their gene transcription levels. Our data suggest that gentle level of cyclic mechanical stretch exerts a protective effect on RA-FLS as it downregulates the level of MMP-1 protease, COX-2, and proinflammatory PGE(2). The underlying mechanism appears to be, in part, executed through NF-kappa B and its upstream effectors.
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