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

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

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.

Original languageEnglish
Article numbere0165922
JournalPLoS One
Volume11
Issue number11
DOIs
Publication statusPublished - 2016 Nov 1

Fingerprint

Selective Estrogen Receptor Modulators
Hypoxia-Inducible Factor 1
osteoclasts
Osteoclasts
mice
estrogens
tamoxifen
Bone
Estrogens
Diphosphonates
Tamoxifen
Proteins
proteins
bones
Bone and Bones
bone resorption
osteoporosis
Bone Resorption
Osteoporosis
Anti-Idiotypic Antibodies

ASJC Scopus subject areas

  • Medicine(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Morita, M., Sato, Y., Iwasaki, R., Kobayashi, T., Watanabe, R., Oike, T., ... Miyamoto, T. (2016). Selective estrogen receptor modulators suppress Hif1α protein accumulation in mouse osteoclasts. PLoS One, 11(11), [e0165922]. https://doi.org/10.1371/journal.pone.0165922

Selective estrogen receptor modulators suppress Hif1α protein accumulation in mouse osteoclasts. / Morita, Mayu; Sato, Yuiko; Iwasaki, Ryotaro; Kobayashi, Tami; Watanabe, Ryuichi; Oike, Takatsugu; Miyamoto, Kana; Toyama, Yoshiaki; Matsumoto, Morio; Nakamura, Masaya; Kawana, Hiromasa; Nakagawa, Taneaki; Miyamoto, Takeshi.

In: PLoS One, Vol. 11, No. 11, e0165922, 01.11.2016.

Research output: Contribution to journalArticle

Morita, M, Sato, Y, Iwasaki, R, Kobayashi, T, Watanabe, R, Oike, T, Miyamoto, K, Toyama, Y, Matsumoto, M, Nakamura, M, Kawana, H, Nakagawa, T & Miyamoto, T 2016, 'Selective estrogen receptor modulators suppress Hif1α protein accumulation in mouse osteoclasts', PLoS One, vol. 11, no. 11, e0165922. https://doi.org/10.1371/journal.pone.0165922
Morita M, Sato Y, Iwasaki R, Kobayashi T, Watanabe R, Oike T et al. Selective estrogen receptor modulators suppress Hif1α protein accumulation in mouse osteoclasts. PLoS One. 2016 Nov 1;11(11). e0165922. https://doi.org/10.1371/journal.pone.0165922
Morita, Mayu ; Sato, Yuiko ; Iwasaki, Ryotaro ; Kobayashi, Tami ; Watanabe, Ryuichi ; Oike, Takatsugu ; Miyamoto, Kana ; Toyama, Yoshiaki ; Matsumoto, Morio ; Nakamura, Masaya ; Kawana, Hiromasa ; Nakagawa, Taneaki ; Miyamoto, Takeshi. / Selective estrogen receptor modulators suppress Hif1α protein accumulation in mouse osteoclasts. In: PLoS One. 2016 ; Vol. 11, No. 11.
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