Treatment with an active vitamin D analogue blocks hypothalamic dysfunction-induced bone loss in mice

Eri Ito, Yuiko Sato, Tami Kobayashi, Satoshi Nakamura, Yosuke Kaneko, Tomoya Soma, Tatsuaki Matsumoto, Atushi Kimura, Kana Miyamoto, Hideo Matsumoto, Morio Matsumoto, Masaya Nakamura, Kazuki Sato, Takeshi Miyamoto

研究成果: Article査読

抄録

Estrogen deficiency can be caused by ovarian dysfunction in females. Mechanisms underlying osteoporosis in this condition have been characterized in animal models, such as ovariectomized mice and rats, although it remains unclear how hypothalamic dysfunction promotes osteoporosis. Here, we show that administration of a gonadotropin-releasing hormone antagonist (GnRHa) significantly decreases uterine weight, a manifestation of hypothalamic dysfunction, and promotes both cortical and trabecular bone loss in female mice in vivo. We also report that osteoclast number significantly increased in mice administered GnRHa, and that the transcription factor hypoxia inducible factor 1 alpha (HIF1α) accumulated in those osteoclasts. We previously reported that treatment of mice with the active vitamin D analogue ED71, also known as eldecalcitol, inhibited HIF1α accumulation in osteoclasts. We show here that in mice, co-administration of ED71 with GnRHa significantly rescued the reduced cortical and trabecular bone mass promoted by GnRHa administration alone. GnRHa-dependent HIF1α accumulation in osteoclasts was also blocked by co-administration of ED71. We conclude that hypothalamic dysfunction promotes HIF1α accumulation in osteoclasts and likely results in reduced bone mass. We conclude that treatment with ED71 could serve as a therapeutic option to counter osteoporotic conditions in humans.

本文言語English
ページ(範囲)48-53
ページ数6
ジャーナルBiochemical and Biophysical Research Communications
542
DOI
出版ステータスPublished - 2021 2月 26

ASJC Scopus subject areas

  • 生物理学
  • 生化学
  • 分子生物学
  • 細胞生物学

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