Selective estrogen receptor modulators suppress Hif1α protein accumulation in mouse osteoclasts

Mayu Morita, Yuiko Sato, Ryotaro Iwasaki, Tami Kobayashi, Ryuichi Watanabe, Takatsugu Oike, Kana Miyamoto, Yoshiaki Toyama, Morio Matsumoto, Masaya Nakamura, Hiromasa Kawana, Taneaki Nakagawa, Takeshi Miyamoto

研究成果: Article査読

12 被引用数 (Scopus)

抄録

Anti-bone resorptive drugs such as bisphosphonates, the anti-RANKL antibody (denosu-mab), or selective estrogen receptor modulators (SERMs) have been developed to treat osteoporosis. Mechanisms underlying activity of bisphosphonates or denosumab in this context are understood, while it is less clear how SERMs like tamoxifen, raloxifene, or bazedoxifene inhibit bone resorption. Recently, accumulation of hypoxia inducible factor 1 alpha (Hif1α) in osteoclasts was shown to be suppressed by estrogen in normal cells. In addition, osteoclast activation and decreased bone mass seen in estrogen-deficient conditions was found to require Hif1α. Here, we used western blot analysis of cultured osteoclast precursor cells to show that tamoxifen, raloxifene, or bazedoxifene all suppress Hif1 α protein accumulation. The effects of each SERM on osteoclast differentiation differed in vitro. Our results suggest that interventions such as the SERMs evaluated here could be useful to inhibit Hif1α and osteoclast activity under estrogen-deficient conditions.

本文言語English
論文番号e0165922
ジャーナルPloS one
11
11
DOI
出版ステータスPublished - 2016 11月

ASJC Scopus subject areas

  • 生化学、遺伝学、分子生物学(全般)
  • 農業および生物科学(全般)
  • 一般

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