title: The delayed recovery of the remobilized rat tibialis anterior muscle reflects a defect in proliferative and terminal differentiation that impairs early regenerative processes.
abstract: BACKGROUND
  The immobilization-induced tibialis anterior (TA) muscle atrophy worsens after cast removal and is associated with altered extracellular matrix (ECM) composition. The secreted protein acidic and rich in cysteine (Sparc) is an ECM component involved in Akt activation and in β-catenin stabilization, which controls protein turnover and induces muscle regulatory factors (MRFs), respectively. We hypothesized that ECM alterations may influence these intracellular signalling pathways controlling TA muscle mass.
  
  
  METHODS
  Six-month-old Wistar rats were subjected to hindlimb cast immobilization for 8 days (I8) or not (I0) and allowed to recover for 1 to 10 days (R1-10).
  
  
  RESULTS
  The TA atrophy during remobilization correlated with reduced fibre cross-sectional area and thickening of endomysium. mRNA levels for Sparc increased during remobilization until R10 and for integrin-α7 and -β1 at I8 and R1. Integrin-linked kinase protein levels increased during immobilization and remobilization until R10. This was inversely correlated with changes in Akt phosphorylation. β-Catenin protein levels increased in the remobilized TA at R1 and R10. mRNA levels of the proliferative MRFs (Myf5 and MyoD) increased at I8 and R1, respectively, without changes in Myf5 protein levels. In contrast, myogenin mRNA levels (a terminal differentiation MRF) decreased at R1, but only increased at R10 in remobilized muscles, as for protein levels.
  
  
  CONCLUSIONS
  Altogether, this suggests that the TA inefficiently attempted to preserve regeneration during immobilization by increasing transcription of proliferative MRFs, and that the TA could engage recovery during remobilization only when the terminal differentiation step of regeneration is enhanced.
authors.affiliation: INRA, UMR 1019, UNH, CRNH, F-63000, Auvergne, Clermont-Ferrand, France.|Clermont Université, Université d'Auvergne, Unité de Nutrition Humaine, BP 10448, F-63000, Clermont-Ferrand, France.
authors.forename: Lamia
authors.initials: L
authors.lastname: Slimani
authors.affiliation: Centre Hospitalier Universitaire, 63000, Clermont-Ferrand, France.
authors.forename: Emilie
authors.initials: E
authors.lastname: Vazeille
authors.affiliation: INRA, UMR 1019, UNH, CRNH, F-63000, Auvergne, Clermont-Ferrand, France.|Clermont Université, Université d'Auvergne, Unité de Nutrition Humaine, BP 10448, F-63000, Clermont-Ferrand, France.
authors.forename: Christiane
authors.initials: C
authors.lastname: Deval
authors.affiliation: INRA, UMR 1213 Herbivores, 63122, Saint Genès Champanelle, France.
authors.forename: Bruno
authors.initials: B
authors.lastname: Meunier
authors.affiliation: INRA, UMR 1019, UNH, CRNH, F-63000, Auvergne, Clermont-Ferrand, France.|Clermont Université, Université d'Auvergne, Unité de Nutrition Humaine, BP 10448, F-63000, Clermont-Ferrand, France.
authors.forename: Cécile
authors.initials: C
authors.lastname: Polge
authors.affiliation: INRA, UMR 1019, UNH, CRNH, F-63000, Auvergne, Clermont-Ferrand, France.|Clermont Université, Université d'Auvergne, Unité de Nutrition Humaine, BP 10448, F-63000, Clermont-Ferrand, France.
authors.forename: Dominique
authors.initials: D
authors.lastname: Dardevet
authors.affiliation: INRA, UMR 1019, UNH, CRNH, F-63000, Auvergne, Clermont-Ferrand, France.|Clermont Université, Université d'Auvergne, Unité de Nutrition Humaine, BP 10448, F-63000, Clermont-Ferrand, France.
authors.forename: Daniel
authors.initials: D
authors.lastname: Béchet
authors.affiliation: INRA, UMR 1019, UNH, CRNH, F-63000, Auvergne, Clermont-Ferrand, France.|Clermont Université, Université d'Auvergne, Unité de Nutrition Humaine, BP 10448, F-63000, Clermont-Ferrand, France.
authors.forename: Daniel
authors.initials: D
authors.lastname: Taillandier
authors.affiliation: INRA, UMR 1213 Herbivores, 63122, Saint Genès Champanelle, France.
authors.forename: Didier
authors.initials: D
authors.lastname: Micol
authors.affiliation: INRA, UMR 1213 Herbivores, 63122, Saint Genès Champanelle, France.
authors.forename: Anne
authors.initials: A
authors.lastname: Listrat
authors.affiliation: INRA, UMR 1019, UNH, CRNH, F-63000, Auvergne, Clermont-Ferrand, France.|Clermont Université, Université d'Auvergne, Unité de Nutrition Humaine, BP 10448, F-63000, Clermont-Ferrand, France.
authors.forename: Didier
authors.initials: D
authors.lastname: Attaix
authors.affiliation: INRA, UMR 1019, UNH, CRNH, F-63000, Auvergne, Clermont-Ferrand, France.|Clermont Université, Université d'Auvergne, Unité de Nutrition Humaine, BP 10448, F-63000, Clermont-Ferrand, France.
authors.forename: Lydie
authors.initials: L
authors.lastname: Combaret
keywords: Extracellular matrix; Outside‐In signaling; Recovery; Regeneration; Skeletal muscle atrophy; β‐Catenin