Receptor activator of nuclear factor κB ligand (RANKL) plays a crucial role in the bone erosion of rheumatoid arthritis (RA) by prompting osteoclastogenesis. Considering that 1,25(OH)2D3 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)2D3 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 IL1β and then treated with different concentrations of 1,25(OH)2D3 for 48？h. A significantly elevated OPG/RANKL ratio and markedly decreased levels of IL-6 and TNFβ mRNA expression in cells and IL-6 protein in supernatants were observed in IL1β-induced MH7A in the presence of 1,25(OH)2D3 compared with those in the absence of it. Osteoclast formation was obviously decreased when RAW264.7 cells were treated with both 1,25(OH)2D3 and IL1β. In summary, although it has a biological function to induce RANKL expression, 1,25(OH)2D3 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. 1. Introduction Rheumatoid arthritis (RA) is the most common systemic autoimmune disease affecting approximately 1% of the population worldwide. The persistent synovitis and thereby bone erosion are the hallmark of RA. Though the precise etiology of RA still remains elusive, osteoclast, formed by fusion of mononuclear precursors of the monocyte/macrophage, is the cell ultimately responsible for bone destruction in RA [1]. The past decade has witnessed a number of regulators of osteoclast differentiation and function. Among them, receptor activator of nuclear factor κB ligand (RANKL) plays the most important role in osteoclast development, activity, and survival [2]. It has been previously reported that mice deficient in RANKL are protected from bone erosion in a serum transfer model of arthritis [3]. In RA patients, local and systemic increased RANKL levels are associated with bone resorption, suggesting their pivotal role in mediating bone erosion [4]. RANKL exerts its functions by binding to its unique receptor RANK, and osteoprotegerin (OPG) acts as its natural decoy receptor by blocking the RANK/RANKL interaction. Mice lacking OPG exhibit severe osteoporosis and bone erosions [5], implicating the importance of
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