Smad2 and Smad3 expressed in skeletal muscle promote immobilization-induced bone atrophy in mice

Taro Umezu, Satoshi Nakamura, Yuiko Sato, Tami Kobayashi, Eri Ito, Takaya Abe, Mari Kaneko, Masatoshi Nomura, Akihiko Yoshimura, Akihito Oya, Morio Matsumoto, Masaya Nakamura, Arihiko Kanaji, Takeshi Miyamoto

Research output: Contribution to journalArticlepeer-review

Abstract

Skeletal muscle is known to regulate bone homeostasis through muscle-bone interaction, although factors that control this activity remain unclear. Here, we newly established Smad3-flox mice, and then generated skeletal muscle-specific Smad2/Smad3 double conditional knockout mice (DcKO) by crossing Smad3-flox with skeletal muscle-specific Ckmm Cre and Smad2-flox mice. We show that immobilization-induced gastrocnemius muscle atrophy occurring due to sciatic nerve denervation was partially but significantly inhibited in DcKO mice, suggesting that skeletal muscle cell-intrinsic Smad2/3 is required for immobilization-induced muscle atrophy. Also, tibial bone atrophy seen after sciatic nerve denervation was partially but significantly inhibited in DcKO mice. Bone formation rate in wild-type mouse tibia was significantly inhibited by immobilization, but inhibition was abrogated in DcKO mice. We propose that skeletal muscle regulates immobilization-induced bone atrophy via Smad2/3, and Smad2/3 represent potential therapeutic targets to prevent both immobilization-induced bone and muscle atrophy.

Original languageEnglish
Pages (from-to)111-117
Number of pages7
JournalBiochemical and Biophysical Research Communications
Volume582
DOIs
Publication statusPublished - 2021 Dec 10

Keywords

  • Atrophy
  • Bone
  • Immobilization
  • Skeletal muscle
  • Smad2
  • Smad3

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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