The Effects Of Increasing Concentration Of Adiponectin Isoforms On The Proinflammatory Effect Of Rheumatoid Arthritis Synovial Fibroblasts

Objective: 1. To investigate whether the adiponectin isoforms differentially affect the expression of relative inflammatory factors of rheumatoid arthritis synovial fibroblasts(RASF); 2. To investigate the relations between the concentration of individual adiponectin isoforms and the production of the inflammatory factors of RASF.Methods: Articular synovial tissues were obtained from the patients fulfilled with diagnostic criteria of rheumatoid arthritis(RA), and healthy people. RASF and human fibroblast-like synoviocytes(HFLS) were isolated and cultured. Fibroblasts from passages four to five were used for the experiments.They were stimulated with increasing concentrations of 25μg/ml, 50μg/ml, and 100μg/ml of different human adiponectin isoforms for 15 h. The levels of matrix metalloproteinases(MMP)-3,MMP-10, tumor necrosis factor(TNF)-α, vascular endothelial growth factor(VEGF), and prostaglandin E2(PGE2) in culture supernatants were measured by immunoassays.Results: All adiponectin isoforms can increase the expression of MMP-3, MMP-10, TNF-α, VEGF and PGE2 of RASF and HFLS at 5μg/ml,50μg/ml, and 100μg/ml. In addition, these up-regulated levels ofinflammatory factors have statistical significance in comparison to unstimulated RASF(p<0.01) and HFLS(p<0.05) which were treated with the same conditions. The treatment of RASF and HFLS with three adiponectin isoforms resulted in a dose-dependent increase in all the inflammatory factors expression. And the effect of HMW(high molecular weight)/ MMW(middle molecular weight) adiponectin is the strongest among them.Conclusions: 1. All adiponectin isoforms may contribute to proinflammatory effect by stimulating the production of MMP-3,MMP-10, TNF-α, VEGF and PGE2 in RASF, and the effect of HMW/MMW is the strongest among them; 2. HMW/MMW adiponectin could play an important role in arthral matrix destroying and synovial vascular creating of the pathology of RA; 3. Reducing the level of adiponectin in synovial fluid, especially the HMW/MMW isoform, may be a new therapy for RA.