期刊
JOURNAL OF BONE AND MINERAL METABOLISM
卷 27, 期 6, 页码 643-652出版社
SPRINGER TOKYO
DOI: 10.1007/s00774-009-0084-4
关键词
Vitamin D; Osteoclastogenesis; NFATc1; IFN-beta; 1 alpha,25(OH)(2)D-3
资金
- Precursory Research for Embryonic Science and Technology
- Japan Science and Technology Agency
- Japan Society for the Promotion of Science Fujita Memorial Fund for Medical Research
- Ministry of Education, Culture, Sports, Science and Technology, Japan
1-Alpha, 25-dihydroxy vitamin D-3 (1 alpha,25(OH)(2)D-3), an active form of vitamin D-3, plays a critical role in calcium and bone metabolism. Although 1 alpha,25(OH)(2)D-3 has been used for osteoporosis therapy, the direct role of 1 alpha,25(OH)(2)D-3 on human osteoclastogenesis has not been well characterized. Here we show that 1 alpha,25(OH)(2)D-3 treatment significantly inhibited human osteoclast formation at the early stage of differentiation in a concentration-dependent manner. 1 alpha,25(OH)(2)D-3 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-beta (IFN-beta), a strong inhibitor of osteoclastogenesis in osteoclast progenitors. Inhibitory effects of 1 alpha,25(OH)(2)D-3 on osteoclastogenesis and NFATc1 expression were restored by treatment with an antibody against IFN-beta, suggesting that upregulation of IFN-beta by 1 alpha,25(OH)(2)D-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 1 alpha,25(OH)(2)D-3 through regulation of the IFN-beta and NFATc1 axis.
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