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

Research output: Contribution to journalArticle

44 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)643-652
Number of pages10
JournalJournal of Bone and Mineral Metabolism
Volume27
Issue number6
DOIs
Publication statusPublished - 2009 Nov
Externally publishedYes

Keywords

  • 1α,25(OH) D
  • IFN-β
  • NFATc1
  • Osteoclastogenesis
  • Vitamin D

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Orthopedics and Sports Medicine
  • Endocrinology

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    Sakai, S., Takaishi, H., Matsuzaki, K., Kaneko, H., Furukawa, M., Miyauchi, Y., Shiraishi, A., Saito, K., Tanaka, A., Taniguchi, T., Suda, T., Miyamoto, T., & Toyama, Y. (2009). 1-Alpha, 25-dihydroxy vitamin D3 inhibits osteoclastogenesis through IFN-beta-dependent NFATc1 suppression. Journal of Bone and Mineral Metabolism, 27(6), 643-652. https://doi.org/10.1007/s00774-009-0084-4