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

Sadaoki Sakai, Hironari Takaishi, Kenichiro Matsuzaki, Hironori Kaneko, Mitsuru Furukawa, Yoshiteru Miyauchi, Ayako Shiraishi, Keiji Saito, Akio Tanaka, Tadatsugu Taniguchi, Toshio Suda, Takeshi Miyamoto, Yoshiaki Toyama

研究成果: Article査読

45 被引用数 (Scopus)

抄録

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.

本文言語English
ページ(範囲)643-652
ページ数10
ジャーナルJournal of Bone and Mineral Metabolism
27
6
DOI
出版ステータスPublished - 2009 11

ASJC Scopus subject areas

  • 内分泌学、糖尿病および代謝内科学
  • 整形外科およびスポーツ医学
  • 内分泌学

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