title: Muscle-specific GSK-3β ablation accelerates regeneration of disuse-atrophied skeletal muscle.
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-3β deletion facilitates the recovery of disuse-atrophied skeletal muscle. Wild-type mice and mice lacking muscle GSK-3β (MGSK-3β 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-3β KO muscle. Reloading-associated changes in muscle protein turnover were not affected by GSK-3β 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-3β. This study demonstrates that muscle mass recovery and post-natal myogenesis from disuse-atrophy are accelerated in the absence of GSK-3β.
authors.affiliation: The Department of Respiratory Medicine, School for Nutrition and Translational Research in Metabolism (NUTRIM), Maastricht University Medical Centre (MUMC(+)), Maastricht, the Netherlands.
authors.forename: Nicholas A M
authors.initials: NA
authors.lastname: Pansters
authors.affiliation: The Department of Respiratory Medicine, School for Nutrition and Translational Research in Metabolism (NUTRIM), Maastricht University Medical Centre (MUMC(+)), Maastricht, the Netherlands.
authors.forename: Annemie M W J
authors.initials: AM
authors.lastname: Schols
authors.affiliation: The Department of Respiratory Medicine, School for Nutrition and Translational Research in Metabolism (NUTRIM), Maastricht University Medical Centre (MUMC(+)), Maastricht, the Netherlands.
authors.forename: Koen J P
authors.initials: KJ
authors.lastname: Verhees
authors.affiliation: The Department of Respiratory Medicine, School for Nutrition and Translational Research in Metabolism (NUTRIM), Maastricht University Medical Centre (MUMC(+)), Maastricht, the Netherlands.
authors.forename: Chiel C
authors.initials: CC
authors.lastname: de Theije
authors.affiliation: The Department of Respiratory Medicine, School for Nutrition and Translational Research in Metabolism (NUTRIM), Maastricht University Medical Centre (MUMC(+)), Maastricht, the Netherlands.
authors.forename: Frank J
authors.initials: FJ
authors.lastname: Snepvangers
authors.affiliation: The Department of Respiratory Medicine, School for Nutrition and Translational Research in Metabolism (NUTRIM), Maastricht University Medical Centre (MUMC(+)), Maastricht, the Netherlands.
authors.forename: Marco C J M
authors.initials: MC
authors.lastname: Kelders
authors.affiliation: The Department of Respiratory Medicine, School for Nutrition and Translational Research in Metabolism (NUTRIM), Maastricht University Medical Centre (MUMC(+)), Maastricht, the Netherlands.
authors.forename: Niki D J
authors.initials: ND
authors.lastname: Ubags
authors.affiliation: The Department of Respiratory Medicine, School for Nutrition and Translational Research in Metabolism (NUTRIM), Maastricht University Medical Centre (MUMC(+)), Maastricht, the Netherlands.
authors.forename: Astrid
authors.initials: A
authors.lastname: Haegens
authors.affiliation: The Department of Respiratory Medicine, School for Nutrition and Translational Research in Metabolism (NUTRIM), Maastricht University Medical Centre (MUMC(+)), Maastricht, the Netherlands. Electronic address: r.langen@maastrichtuniversity.nl.
authors.forename: Ramon C J
authors.initials: RC
authors.lastname: Langen
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D038362:Glycogen Synthase Kinase 3 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D000071679:Glycogen Synthase Kinase 3 beta; D007334:Insulin-Like Growth Factor I / Q000235:genetics / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D024510:Muscle Development; D009124:Muscle Proteins / Q000235:genetics / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000502:physiology*; D009133:Muscular Atrophy / Q000201:enzymology* / Q000235:genetics / Q000473:pathology / Q000503:physiopathology; D012038:Regeneration
chemical_list: D009124:Muscle Proteins; D007334:Insulin-Like Growth Factor I; D000071679:Glycogen Synthase Kinase 3 beta; C000605507:Gsk3b protein, mouse; D038362:Glycogen Synthase Kinase 3
keywords: Akt/mTOR; Disuse-atrophy; FoXO/atrogin/MuRF1; Hindlimb suspension/reloading; Muscle regeneration; MyoD/myogenin