Smad2 and Smad3 expressed in skeletal muscle promote immobilization-induced bone atrophy in mice.
Biochem Biophys Res Commun
; 582: 111-117, 2021 12 10.
Article
em En
| MEDLINE
| ID: mdl-34710825
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.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Nervo Isquiático
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Atrofia Muscular
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Músculo Esquelético
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Proteína Smad2
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Proteína Smad3
Limite:
Animals
Idioma:
En
Revista:
Biochem Biophys Res Commun
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
Japão