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Adiponectin receptor 1 mediates the difference in adiponectin-induced prostaglandin E2 production in rheumatoid arthritis and osteoarthritis synovial fibroblasts
Authors:Zuo Wei  Wu Zhi-Hong  Wu Nan  Duan Yuan-Hui  Wu Ju-Tai  Wang Hai  Qiu Gui-Xing
Affiliation:Department of Orthopedics, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China
Abstract:Background The synovial fluid concentrations of adiponectin are significantly higher in patients with rheumatoid arthritis (RA) than in patients with osteoarthritis (OA).Accumulating evidence suggests that adiponectin may be an inducer of inflammation in arthritis,but the mechanism remains unclear.The objectives of this study were to compare the expression levels of adiponectin receptors in rheumatoid arthritis synovial fibroblasts (RASF) and osteoarthritis synovial fibroblasts (OASF),evaluate the roles of adiponectin receptors in adiponectin-induced prostaglandin E2 (PGE2) production,and then investigate the effects of a nonsteroidal anti-inflammatory drug (NSAID) and a cyclooxygenase (COX)-2-selective inhibitor on adiponectin-induced PGE2 release.Methods The expressions of adiponectin receptor 1 (AdipoR1) and AdipoR2 mRNA and protein in synovial fibroblasts from seven patients with RA and eight patients with OA undergoing total knee replacement were evaluated by real-time polymerase chain reaction,immunofluorescence microscopy and Western blotting analysis.Adiponectin-induced PGE2 production was detected by enzyme-linked immunosorbent assay.RNA interference against the AdipoR1 and AdipoR2 genes was performed to investigate the effects of the adiponectin receptors on adiponectin-induced PGE2 production in both RASF and OASF.Results AdipoR1 and AdipoR2 mRNA and protein were expressed by both RASF and OASF.Compared with OASF,RASF exhibited higher levels of AdipoR1,but there was no significant difference for AdipoR2.Adiponectin induced the production of PGE2 by the synovial fibroblasts in a concentration-dependent manner,and this was more obvious in RASF.RNA interference showed that the difference may be mediated by the diverse distribution of AdipoR1.The adiponectin-induced PGE2 production was efficiently relieved by the NSAID and COX-2-selective inhibitor.Conclusion The present findings suggest that AdipoR1 may mediate the difference in adiponectin-induced PGE2 production in RASF and OASF.
Keywords:adiponectin  rheumatoid arthritis  osteoarthritis  prostaglandin E2  fibroblast
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