Cyr61 promotes proliferation of fibroblast-like synoviocytes in rheumatoid arthritis and its regulation by inflammatory factor

Objective:To investigate the effect of Cyr61 on the proliferation of Fibroblast-like Synoviocytes(FLS) in rheumatoid arthritis(RA).Methods:Cyr61 expression in synovial tissues(ST) and FLS was examined using Real-time PCR,Western blot and immunohistochemistry simultaneously.FLS were isolated from synovial tissue of RA patients and cultured in vitro.The proliferation of FLS stimulated with synovial fluid(SF) was determined by 3 H-TdR incorporation.Cyr61 protein level in RA SF was detected by ELISA.Results:Cyr61 was over expressed in ST,FLS of RA patients while hardly examined in normal individuals and osterarthritis(OA) patients.Meanwhile,Cyr61 protein level was elevated in SF,which promoted the proliferation of RA FLS.This proliferation was abrogated by knockdown the Cyr61 gene of FLS or neutralizing monoclonal antibody against human Cyr61.Moreover,inflammatory factor IFN-γ and TNF-α up-regulated the expression of Cyr61.Conclusion:These results indicate that the elevated level of IFN-γ and TNF-α in RA SF can promote the proliferation of the FLS derived from RA patients by increasing expression of Cyr61,suggesting that Cyr61 may play an important role in the development of RA.