破骨细胞
化学
秩配基
细胞生物学
内分泌学
骨吸收
骨重建
体外
内科学
骨髓
细胞分化
生物
受体
生物化学
医学
基因
兰克尔
激活剂(遗传学)
作者
So Yeon Kim,Bitnara Lee,Euna Kwon,Choong Hyeok Choi,Il Hoon Sung,Yong-Jin Kim,Jeongwon Sohn,Jong Dae Ji
标识
DOI:10.1016/j.jbspin.2012.09.011
摘要
1,25-dihydroxyvitamin D3 (1,25(OH)2D3) is a key molecule to maintain calcium homeostasis and bone metabolism. It was recently reported that 1,25(OH)2D3 directly inhibited osteoclast differentiation in mouse bone marrow cells and human bone marrow-derived colony-forming unit granulocyte macrophage (CFU-GM) cells. However, the direct effects of 1,25(OH)2D3 and its affecting mechanisms on the osteoclast differentiation of human osteoclast precursors remain largely unknown. In this study, we examined the direct effects of 1,25(OH)2D3 on the osteoclastogenesis of human peripheral blood (PB) osteoclast precursors. In vitro osteoclastogenesis assays were performed using osteoclast precursors from normal PB. The gene expressions were analyzed using real-time PCR. The cell surface proteins, including c-Fms and RANK, were measured by flow cytometry. 1,25(OH)2D3 strongly inhibited osteoclast differentiation and it suppressed the expression of RANK in the human PB osteoclast precursors. One mechanism of RANK inhibition by 1,25(OH)2D3 is down-regulation of the M-CSF receptor c-Fms, which is required for the expression of RANK. In contrast to the previous reports on mouse osteoclast precursors, 1,25(OH)2D3 did not affect the expression of c-Fos. Parallel to the inhibition of osteoclastogenesis, 1,25(OH)2D3 increased the expression and phosphorylation of CCAAT enhancer-binding protein β (C/EBPβ), which is a recently discovered inhibitor of osteoclastogenesis. Our results show that 1,25(OH)2D3 inhibits human osteoclastogenesis by decreasing the RANK+ osteoclast precursors, and we suggest that 1,25(OH)2D3 may be a powerful therapeutic agent for treating inflammation-induced bone disease that shows excessive osteoclast activation.
科研通智能强力驱动
Strongly Powered by AbleSci AI