Methotrexate inhibits osteoclastogenesis by decreasing RANKL-induced calcium influx into osteoclast progenitors

Hiroya Kanagawa, Ritsuko Masuyama, Mayu Morita, Yuiko Sato, Yasuo Niki, Tami Kobayashi, Eri Katsuyama, Atsuhiro Fujie, Wu Hao, Toshimi Tando, Ryuichi Watanabe, Kana Miyamoto, Hideo Morioka, Morio Matsumoto, Yoshiaki Toyama, Hideyuki Saya, Takeshi Miyamoto

研究成果: Article査読

17 被引用数 (Scopus)

抄録

The increasing number of osteoporosis patients is a pressing issue worldwide. Osteoporosis frequently causes fragility fractures, limiting activities of daily life and increasing mortality. Many osteoporosis patients take numerous medicines due to other health issues; thus, it would be preferable if a single medicine could ameliorate osteoporosis and other conditions. Here, we screened 96 randomly selected drugs targeting various diseases for their ability to inhibit differentiation of osteoclasts, which play a pivotal role in development of osteoporosis, and identified methotrexate (MTX), as a potential inhibitor. MTX is currently used to treat sarcomas or leukemic malignancies or auto-inflammatory diseases such as rheumatoid arthritis (RA) through its anti-proliferative and immunosuppressive activities; however, a direct effect on osteoclast differentiation has not been shown. Here, we report that osteoclast formation and expression of osteoclastic genes such as NFATc1 and DC-STAMP, which are induced by the cytokine RANKL, are significantly inhibited by MTX. We found that RANKL-dependent calcium (Ca) influx into osteoclast progenitors was significantly inhibited by MTX. RA patients often develop osteoporosis, and osteoclasts are reportedly required for joint destruction; thus, MTX treatment could have a beneficial effect on RA patients exhibiting high osteoclast activity by preventing both osteoporosis and joint destruction.

本文言語English
ページ(範囲)526-531
ページ数6
ジャーナルJournal of Bone and Mineral Metabolism
34
5
DOI
出版ステータスPublished - 2016 9 1

ASJC Scopus subject areas

  • 内分泌学、糖尿病および代謝内科学
  • 整形外科およびスポーツ医学
  • 内分泌学

フィンガープリント

「Methotrexate inhibits osteoclastogenesis by decreasing RANKL-induced calcium influx into osteoclast progenitors」の研究トピックを掘り下げます。これらがまとまってユニークなフィンガープリントを構成します。

引用スタイル