TY - JOUR
T1 - 1-Alpha, 25-dihydroxy vitamin D3 inhibits osteoclastogenesis through IFN-beta-dependent NFATc1 suppression
AU - Sakai, Sadaoki
AU - Takaishi, Hironari
AU - Matsuzaki, Kenichiro
AU - Kaneko, Hironori
AU - Furukawa, Mitsuru
AU - Miyauchi, Yoshiteru
AU - Shiraishi, Ayako
AU - Saito, Keiji
AU - Tanaka, Akio
AU - Taniguchi, Tadatsugu
AU - Suda, Toshio
AU - Miyamoto, Takeshi
AU - Toyama, Yoshiaki
N1 - Funding Information:
We thank Y. Sato for technical support. T. Miyamoto was supported by 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, and a grant-in-aid from the Global COE Program of the Ministry of Education, Culture, Sports, Science and Technology, Japan, to Keio University.
PY - 2009/11
Y1 - 2009/11
N2 - 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.
AB - 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.
KW - 1α,25(OH) D
KW - IFN-β
KW - NFATc1
KW - Osteoclastogenesis
KW - Vitamin D
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U2 - 10.1007/s00774-009-0084-4
DO - 10.1007/s00774-009-0084-4
M3 - Article
C2 - 19449179
AN - SCOPUS:70449522251
SN - 0914-8779
VL - 27
SP - 643
EP - 652
JO - Journal of Bone and Mineral Metabolism
JF - Journal of Bone and Mineral Metabolism
IS - 6
ER -
