Selective Estrogen Receptor Modulators Suppress Hif1α Protein Accumulation in Mouse Osteoclasts.

Abstract

Anti-bone resorptive drugs such as bisphosphonates, the anti-RANKL antibody (denosumab), 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 Hif1α 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.

• Authors: 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
• Journal: PloS one (PLoS One) Vol. 11 Issue 11 Pg. e0165922 ( 2016) ISSN: 1932-6203 [Electronic] United States
• PMID: 27802325 (Publication Type: Journal Article)

Chemical References

• Hif1a protein, mouse
• Hypoxia-Inducible Factor 1, alpha Subunit
• Selective Estrogen Receptor Modulators
• Tamoxifen

Topics

• Animals
• Bone Resorption (drug therapy)
• Cell Differentiation (drug effects)
• Cell Hypoxia (drug effects)
• Hypoxia-Inducible Factor 1, alpha Subunit (metabolism)
• Mice
• Mice, Inbred C57BL
• Osteoclasts (cytology, drug effects, metabolism)
• Protein Transport (drug effects)
• Selective Estrogen Receptor Modulators (pharmacology, therapeutic use)
• Tamoxifen (pharmacology, therapeutic use)