Modulatory Effect of 1,25-Dihydroxyvitamin D3 on IL1β-Induced RANKL, OPG, TNFα, and IL-6 Expression in Human Rheumatoid Synoviocyte MH7A

Receptor activator of nuclear factor kappa B ligand (RANKL) plays a crucial role in the bone erosion of rheumatoid arthritis (RA) by prompting osteoclastogenesis. Considering that 1,25(OH)(2)D-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)(2)D-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 IL1 beta and then treated with different concentrations of 1,25(OH)(2)D-3 for 48 h. A significantly elevated OPG/RANKL ratio and markedly decreased levels of IL-6 and TNF beta mRNA expression in cells and IL-6 protein in supernatants were observed in IL1 beta-induced MH7A in the presence of 1,25(OH)(2)D-3 compared with those in the absence of it. Osteoclast formation was obviously decreased when RAW264.7 cells were treated with both 1,25(OH)(2)D-3 and IL1 beta. In summary, although it has a biological function to induce RANKL expression, 1,25(OH)(2)D-3 could upregulate OPG/RANKL ratio and mediate anti-inflammatory action in an inflammatory milieu of synoviocyte, contributing to the inhibition of inflammation-induced osteoclastogenesis in RA.