1, 25(OH)2D3 inhibits osteoclastogenesis by IκB/NF-κB signaling pathway

Abstract

Objective To investigate the role and mechanism of vitamin D and vitamin D receptor (VDR) in various stages of osteoclastogenesis. Methods First, bone marrow derived macrophages (BMMs) were extracted from the bone marrow of the femurs and tibias of C57BL/6 mice, and the BMMs were induced into osteoclasts by receptor activator of nuclear kappa B ligand (RANKL) and macrophage colony-stimulating factor (M-CSF). At the same time, different concentrations of 1, 25(OH)2D3 (0.1, 10 and 1 000 nmol/L) were added to activate VDR. TRAP and FAK staining, pit formation assay, qPCR and Western blotting were performed in this study. Results 1, 25(OH)2D3, as a strong agonist of VDR, effectively activated VDR at a dose of 1 000 nmol/L and inhibited the expression of c-Fos and NFATc1 at mRNA and protein levels at the early stage of osteoclast differentiation, and also inhibited the expression of CtsK and MMP9 at mature stage (P < 0.05). The dose significantly down-regulated the phosphorylation of IκBα (P < 0.05), and thereby suppressed the nuclear translocation and phosphorylation of p65. Conclusion 1, 25(OH)2D3 at 1 000 nmol/L significantly up-regulates the expression of VDR, and activates VDR to inhibit osteoclast differentiation, fusion and bone resorption activity through the IκBα/NF-κB p65 signaling pathway.

Keywords

• vitamin d receptor
• osteoclast
• nf-κb
• 1 25(oh)2d3