Muscle regeneration potential and satellite cell activation profile during recovery following hindlimb immobilization in mice

  • Maria Guitart
    Department of Pulmonology‐Muscle Wasting Cachexia in Chronic Respiratory Diseases Lung Cancer Research Group IMIM‐Hospital del Mar Parc de Salut Mar, Health and Sciences Experimental Department (CEXS) Universitat Pompeu Fabra (UPF) Barcelona Biomedical Research Park (PRBB) Barcelona Spain
  • Josep Lloreta
    Department of Pathology Hospital del Mar, Parc de Salut Mar, Health and Experimental Sciences Department (CEXS) Universitat Pompeu Fabra (UPF) Barcelona Biomedical Research Park (PRBB) Barcelona Spain
  • Laura Mañas‐Garcia
    Department of Pulmonology‐Muscle Wasting Cachexia in Chronic Respiratory Diseases Lung Cancer Research Group IMIM‐Hospital del Mar Parc de Salut Mar, Health and Sciences Experimental Department (CEXS) Universitat Pompeu Fabra (UPF) Barcelona Biomedical Research Park (PRBB) Barcelona Spain
  • Esther Barreiro
    Department of Pulmonology‐Muscle Wasting Cachexia in Chronic Respiratory Diseases Lung Cancer Research Group IMIM‐Hospital del Mar Parc de Salut Mar, Health and Sciences Experimental Department (CEXS) Universitat Pompeu Fabra (UPF) Barcelona Biomedical Research Park (PRBB) Barcelona Spain

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<jats:sec><jats:label /><jats:p>Reduced muscle activity leads to muscle atrophy and function loss in patients and animal models. Satellite cells (SCs) are postnatal muscle stem cells that play a pivotal role in skeletal muscle regeneration following injury. The regenerative potential, satellite cell numbers, and markers during recovery following immobilization of the hindlimb for 7 days were explored. In mice exposed to 7 days of hindlimb immobilization, in those exposed to recovery (7 days, splint removal), and in contralateral control muscles, muscle precursor cells were isolated from all hindlimb muscles (fluorescence‐activated cell sorting, FACS) and SCs, and muscle regeneration were identified using immunofluorescence (gastrocnemius and soleus) and electron microscopy (EM, gastrocnemius). Expression of <jats:italic>ki67</jats:italic>, <jats:italic>pax7</jats:italic>, <jats:italic>myoD</jats:italic>, and <jats:italic>myogenin</jats:italic> was quantified (RT‐PCR) from SC FACS yields. Body and grip strength were determined. Following 7 day hindlimb immobilization, a decline in SCs (FACS, immunofluorescence) was observed together with an upregulation of SC activation markers and signs of muscle regeneration including fusion to existing myofibers (EM). Recovery following hindlimb immobilization was characterized by a program of muscle regeneration events. Hindlimb immobilization induced a decline in SCs together with an upregulation of markers of SC activation, suggesting that fusion to existing myofibers takes place during unloading. Muscle recovery induced a significant rise in muscle precursor cells and regeneration events along with reduced SC activation expression markers and a concomitant rise in terminal muscle differentiation expression. These are novel findings of potential applicability for the treatment of disuse muscle atrophy, which is commonly associated with severe chronic and acute conditions.</jats:p></jats:sec>

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