Muscle-specific GSK-3beta ablation accelerates regeneration of disuse-atrophied skeletal muscle

N.A.M. Pansters, A.M. Schols, K.J. Verhees, C.C. de Theije, F. Snepvangers, M.C.J.M. Kelders, N.D.J. Ubags, A. Haegens, R.C. Langen

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Muscle wasting impairs physical performance, increases mortality and reduces medical intervention efficacy in chronic diseases and cancer. Developing proficient intervention strategies requires improved understanding of the molecular mechanisms governing muscle mass wasting and recovery. Involvement of muscle protein- and myonuclear turnover during recovery from muscle atrophy has received limited attention. The insulin-like growth factor (IGF)-I signaling pathway has been implicated in muscle mass regulation. As glycogen synthase kinase 3 (GSK-3) is inhibited by IGF-I signaling, we hypothesized that muscle-specific GSK-3beta deletion facilitates the recovery of disuse-atrophied skeletal muscle. Wild-type mice and mice lacking muscle GSK-3beta (MGSK-3beta KO) were subjected to a hindlimb suspension model of reversible disuse-induced muscle atrophy and followed during recovery. Indices of muscle mass, protein synthesis and proteolysis, and post-natal myogenesis which contribute to myonuclear accretion, were monitored during the reloading of atrophied muscle. Early muscle mass recovery occurred more rapidly in MGSK-3beta KO muscle. Reloading-associated changes in muscle protein turnover were not affected by GSK-3beta ablation. However, coherent effects were observed in the extent and kinetics of satellite cell activation, proliferation and myogenic differentiation observed during reloading, suggestive of increased myonuclear accretion in regenerating skeletal muscle lacking GSK-3beta. This study demonstrates that muscle mass recovery and post-natal myogenesis from disuse-atrophy are accelerated in the absence of GSK-3beta.
Original languageEnglish
Pages (from-to)490-506
JournalBiochimica et Biophysica Acta. Mucoproteins and Mucopolysaccharides
Volume1852
Issue number3
DOIs
Publication statusPublished - 1 Jan 2015

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