VEGF induces RANKL in Rheumatoid Arthritis synovial fibroblasts

Abstract

BACKGROUDVEGF is the most endothelial cell‐specific angiogenic factor characterised to date. Several recent reports have demonstrated that VEGF is also implicated in the pathogenesis of RA, and serum levels of VEGF correlate well with RA disease activity, particularly with swollen joint counts.OBJECTIVEThis study aims to determine the effect and mechanism of VEGF on bony destructive process in RA through RANKL regulation from synovial fibroblasts.METHODSynovial fibroblasts were isolated from synovial tissues of RA patients. After RA synovial fibroblasts were treated with rhVEGF, the expression of RANKL mRNA was determined using real‐time PCR. After inhibition of pro‐inflammatory cytokines or intracellular signal molecules, the change of the VEGF‐induced RANKL expression was determined using real‐time PCR.RESULTSThe expression of RANKL mRNA in RA synovial fibroblasts was increased after VEGF stimulation in a dose dependent manner. VEGF‐induced RANKL expression was also diminished after inhibition of Src, PKC and ERK.CONCLUSIONOur results show that VEGF upregulates RANKL expression in RA synovial fibroblasts. These effects are mediated by the Src/PKC and ERK pathways.This work was supported by the National Research Foundation of Korea Grant funded by the Korean Government (NRF‐2010‐R1A4A007‐0024198)