Effects Of IL-34 On Fibroblast-like Synoviocytes And Peripheral Blood Mononuclear-cells In Rheumatoid Arthritis

Objective: Rheumatoid arthritis(RA)is a chronic systemic autoimmune disease characterized by chronic synovitis.Bone destruction of joints occurs with progression of disease.Osteoporosis is one of the major complications of RA.Receptor activator of nuclear factor kappa-B ligand(RANKL)/ Osteoprotegerin(OPG)system is the key regulator of bone remodeling,and plays pivotal role in bone destruction in RA.Matrix metalloproteinase(MMP)is one enzyme family that participates in cartilage destruction by degrading extracellular matrix of chondrocytes.RANKL/OPG and MMP-3 are regulated by interleukin(IL)-17.IL-34 is a cytokine which is closely associated with RA and is significantly related to disease progression.IL-34 affects production of IL-17 by different cell groups.This study aims to investigate the effect of IL-34 on fibroblast-like synoviocytes(FLS)and peripheral blood mononuclear cells(PBMC)to regulate production of RANKL,OPG and MMP-3 and whether the effect is mediated by IL-17.Method: RA-FLS and RA-PBMC were treated with rh IL-34(0,10,20,50,100ng/m L),with or without IL-17 inhibitor(Plumbagin).Cell-free supernatants were collected after 72 hours incubation,and the levels of RANKL,OPG and MMP-3 were determined by enzyme-linked immunosorbent assay(ELISA).Results: IL-34 promoted RA-FLS and RA-PBMC expression of RANKL,inhibited expression of OPG,and did not have significant effect on MMP-3 expression.The promotion and inhibition effects were reduced by addition of IL-17 inhibitor.Conclusion: IL-34 may regulate RANKL/OPG expression by RA-FLS and RA-PBMC,and plays an important role in local joint destruction and systemic osteoporosis in RA.