1-Alpha, 25-dihydroxy vitamin D₃ inhibits osteoclastogenesis through IFN-beta-dependent NFATc1 suppression

1-Alpha, 25-dihydroxy vitamin D₃ (1α,25(OH) ₂D₃), an active form of vitamin D₃, plays a critical role in calcium and bone metabolism. Although 1α,25(OH) ₂D₃ has been used for osteoporosis therapy, the direct role of 1α,25(OH)₂D₃ on human osteoclastogenesis has not been well characterized. Here we show that 1α,25(OH) ₂D₃ treatment significantly inhibited human osteoclast formation at the early stage of differentiation in a concentration-dependent manner. 1α,25(OH)₂D₃ inhibited the expression of nuclear factor of activated T cells c1 (NFATc1, also referred as NFAT2), an essential transcription factor for osteoclast differentiation, and upregulated the expression of interferon-β (IFN-β), a strong inhibitor of osteoclastogenesis in osteoclast progenitors. Inhibitory effects of 1α,25(OH)₂D₃ on osteoclastogenesis and NFATc1 expression were restored by treatment with an antibody against IFN-β, suggesting that upregulation of IFN-β by 1α,25(OH)₂D ₃ treatment results in inhibition of NFATc1 expression, in turn interfering with osteoclast formation. Thus, our study may provide a molecular basis for the treatment of human bone diseases by 1α,25(OH) ₂D₃ through regulation of the IFN-β and NFATc1 axis.