Ibandronate concomitantly blocks immobilization-induced bone and muscle atrophy

Ryuichi Watanabe, Nobuyuki Fujita, Satoshi Takeda, Yuiko Sato, Tami Kobayashi, Mayu Morita, Takatsugu Oike, Kana Miyamoto, Yoshihiro Matsumoto, Morio Matsumoto, Masaya Nakamura, Takeshi Miyamoto

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Both bone and muscle volume is concomitantly reduced under immobilization conditions; however, no single drug is currently available to block these outcomes simultaneously. Bisphosphonates are utilized clinically to inhibit osteoclast-dependent bone resorption, but their effects on muscle are largely unknown. Here we show that skeletal muscle is a direct target of the bisphosphonate ibandronate (IBN) and that reduced muscle volume and induction of Atrogin-1 and MuRF1, both atrogenes, are significantly inhibited by IBN administration in vivo using a mouse model of muscle atrophy. IBN treatment also significantly blocked immobilization-induced bone loss in vivo. We also report that expression of Atrogin-1 and MuRF1 and accumulation of Smad2/3 proteins, which are upstream of atrogines, occurred following serum starvation of myogenic C2C12 cells in vitro, effects significantly inhibited by IBN treatment. Interestingly, IBN effects on C2C12 cells were abrogated by MG132, an ubiquitin/proteasome inhibitor, suggesting that IBN functions via the ubiquitin-proteasome system. Our findings lend new insight into the role of IBN in preventing muscle atrophy.

Original languageEnglish
Pages (from-to)662-668
Number of pages7
JournalBiochemical and Biophysical Research Communications
Volume480
Issue number4
DOIs
Publication statusPublished - 2016 Nov 25

Keywords

  • Bisphosphonate
  • Bone loss
  • Ibandronate
  • Immobilization
  • Muscle atrophy
  • Osteoclast

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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  • Cite this

    Watanabe, R., Fujita, N., Takeda, S., Sato, Y., Kobayashi, T., Morita, M., Oike, T., Miyamoto, K., Matsumoto, Y., Matsumoto, M., Nakamura, M., & Miyamoto, T. (2016). Ibandronate concomitantly blocks immobilization-induced bone and muscle atrophy. Biochemical and Biophysical Research Communications, 480(4), 662-668. https://doi.org/10.1016/j.bbrc.2016.10.112