Modulatory Effect of 1,25-Dihydroxyvitamin D_3 on IL1beta-Induced RANKL, OPG, TNFalpha, and IL-6 Expression in Human Rheumatoid Synoviocyte MH7A

摘要

Receptor activator of nuclear factor kappaB ligand (RANKL) plays a crucial role in the bone erosion of rheumatoid arthritis (RA) by prompting osteodastogenesis. Considering that 1,25(OH)_2D_3 has been suggested as a potent inducer of RANKL expression, it should clarify whether vitamin D supplement could result in RANKL overexpression and thereby facilitate excessive osteoclastogenesis and bone resorption in RA. Here, we investigated modulatory effect of 1,25(OH)_2D_3 on the expression of RANKL and its decoy receptor osteoprotegerin (OPG) in an inflammatory condition of human rheumatoid synoviocyte MH7A. MH7A cells were stimulated with IL1beta and then treated with different concentrations of 1,25(OH)_2D_3 for 48 h. A significantly elevated OPG/RANKL ratio and markedly decreased levels of IL-6 and TNFbeta mRNA expression in cells and IL-6 protein in supernatants were observed in IL1beta-induced MH7A in the presence of 1,25(OH)_2D_3 compared with those in the absence of it. Osteoclast formation was obviously decreased when RAW264.7 cells were treated with both L25(OH)_2D_3 and IL1beta. In summary, although it has a biological function to induce RANKL expression, 1,25(OH)_2D_3 could upregulate OPG/RANKL ratio and mediate anti-inflammatory action in an inflammatory milieu of synoviocyte, contributing to the inhibition of inflammation-induced osteodastogenesis in RA.