Adiponectin Promote Synovial Fibroblasts Migration And Invasion In Rheumatoid Arthritis

Objective:Several clinical studies have suggested the adipocytokine adiponectin(AD) is involved in the progression of rheumatoid arthritis. We previously reported that AD can exacerbate the bone erosion in collagen-induced arthritis but the mechanisms remains unclear. The aim of this study was to investigate whether AD could promote synovial fibroblasts(RASFs) migration and invasion in rheumatoid arthritis.Methods:1.To study whether AD could prompt RASFs migration and invasion in RA.- The effect of AD on bone erosion was analyzed by injection of AD into knee-joint of CIA mouse.- The effect of AD on RASFs migration was detected by wound closure motility assay and transwell corning method.- The effect of AD on RASFs invasion was assayed using the matrigel invasion chambers method.- The RASFs were transfected with si AdipoR1 or si AdipoR2 to determine whether the effect of AD on RASFs migration and invasion is depended on its receptors of Adipo R1 or Adipo R2.2.To study whether AD could stimulate MMP-2,MMP-9 expressing in RASFs.- The expression of AD was correlated with the expression of MMP-2,MMP-9 in CIA mouse.-The expression of MMP-2 and MMP-9 in RASFs upon AD stimulation was tested using Real-time PCR and Western blot.- The RASF were transfected with si AdipoR1 or si AdipoR2 to determine whether the effect of AD on MMP-2 and MMP-9 expression in RASFs is depended on its receptors of Adipo R1 or Adipo R2.3.To study the activation PI3K/AKT signaling pathway in RASFs after AD treatment using western blotResults:1.Adiponectin promote RASFs migration and invasion via Adipo R1.AD exacerbate bone destruction in CIA mouse. :AD(10 μg/ml) significantly promote RASF migration and invasion, as compared with none AD treated group..Silencing Adipo R1 could markedly decrease AD-induced migration and invasion of RASFs, as compared with silencing Adipo R2 in RASFe.2.Adiponectin stimulate expressing MMP-2 and MMP-9 in RASFs via AdipoR1 The expression of AD was positive correlated with the expression of MMP-2 and 9 in CIA mouse. Locally injection of AD into the joint of CIA with resulted the higher expression of MMP-2 and 9 in the joint tissue of CIA. The expression of MMP-2and 9 were significantly increased in RASFs after AD(10 μg/ml) stimulation.Silencing Adipo R1 could markedly decrease AD-induced MMP-2 and 9 expression,as compared with silencing Adipo R2 in RASFs.3.Adiponectin activate PI3K/AKT signal pathwayWith the stimulation of AD(10μg/ml) in RASFs, the phosphorylation of P-PI3 K were detected 30 min and 60min; the phosphorylation of P-AKT(308) was found at15 min and 30 min and P-AKT(473) at 30 min and 60 min.Conclusion:1.AD promote RASFs migration and invasion via AdipoR1.2.AD stimulated the expression of MMP-2 and 9 in RASF via a AdipoR1.AD can activateds PI3K/AKT in RASFs pathway in RASFs.