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Citations to this article

c-Fos protein as a target of anti-osteoclastogenic action of vitamin D, and synthesis of new analogs
Hisashi Takasu, … , Etsuro Ogata, Kyoji Ikeda
Hisashi Takasu, … , Etsuro Ogata, Kyoji Ikeda
Published February 1, 2006
Citation Information: J Clin Invest. 2006;116(2):528-535. https://doi.org/10.1172/JCI24742.
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Research Article Bone biology Article has an altmetric score of 4

c-Fos protein as a target of anti-osteoclastogenic action of vitamin D, and synthesis of new analogs

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Abstract

Although active vitamin D drugs have been used for the treatment of osteoporosis, how the vitamin D receptor (VDR) regulates bone cell function remains largely unknown. Using osteoprotegerin-deficient mice, which exhibit severe osteoporosis due to excessive receptor activator of NF-κB ligand/receptor activator of NF-κB (RANKL/RANK) stimulation, we show herein that oral treatment of these mice with 1α,25-dihydroxyvitamin D3 [1α,25(OH)2D3] inhibited bone resorption and prevented bone loss, suggesting that VDR counters RANKL/RANK signaling. In M-CSF–dependent osteoclast precursor cells isolated from mouse bone marrow, 1α,25(OH)2D3 potently and dose-dependently inhibited their differentiation into multinucleate osteoclasts induced by RANKL. Among signaling molecules downstream of RANK, 1α,25(OH)2D3 inhibited the induction of c-Fos protein after RANKL stimulation, and retroviral expression of c-Fos protein abrogated the suppressive effect of 1α,25(OH)2D3 on osteoclast development. By screening vitamin D analogs based on their c-Fos–suppressing activity, we identified a new analog, named DD281, that inhibited bone resorption and prevented bone loss in ovariectomized mice, more potently than 1α,25(OH)2D3, with similar levels of calcium absorption. Thus, c-Fos protein is an important target of the skeletal action of VDR-based drugs, and DD281 is a bone-selective analog that may be useful for the treatment of bone diseases with excessive osteoclastic activity.

Authors

Hisashi Takasu, Atsuko Sugita, Yasushi Uchiyama, Nobuyoshi Katagiri, Makoto Okazaki, Etsuro Ogata, Kyoji Ikeda

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Total citations by year

Year: 2022 2020 2018 2017 2016 2015 2014 2013 2012 2011 2010 2009 2008 2006 Total
Citations: 1 2 4 3 2 2 2 3 3 1 2 2 1 1 29
Citation information
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Citations to this article in year 2014 (2)

Title and authors Publication Year
Vitamin D endocrine system and osteoclasts
N Takahashi, N Udagawa, T Suda
BoneKEy Reports 2014
The Vitamin D Analogue ED71 but Not 1,25(OH)2D3 Targets HIF1α Protein in Osteoclasts
Y Sato, Y Miyauchi, S Yoshida, M Morita, T Kobayashi, H Kanagawa, E Katsuyama, A Fujie, W Hao, T Tando, R Watanabe, K Miyamoto, H Morioka, M Matsumoto, Y Toyama, T Miyamoto, B Smith
PloS one 2014

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