1. Smad2 and Smad3 expressed in skeletal muscle promote immobilization-induced bone atrophy in mice.
- Author
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Umezu, Taro, Nakamura, Satoshi, Sato, Yuiko, Kobayashi, Tami, Ito, Eri, Abe, Takaya, Kaneko, Mari, Nomura, Masatoshi, Yoshimura, Akihiko, Oya, Akihito, Matsumoto, Morio, Nakamura, Masaya, Kanaji, Arihiko, and Miyamoto, Takeshi
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SKELETAL muscle , *MUSCULAR atrophy , *BONE growth , *ATROPHY , *DRUG target , *SCIATIC nerve - 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. • Smad3 flox mice were newly established. • Skeletal muscle specific Smad2/3 conditional knockout (Smad2/3 cKO) were generated. • Smad2/3 cKO are resistant to denervation induced muscle and bone atrophy. • Denervation induced bone atrophy is promoted by Smad2/3 in muscles. [ABSTRACT FROM AUTHOR]
- Published
- 2021
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