Satellite Cell Depletion Impacts Skeletal Muscle Recovery Following a Burn Injury

Abstract

Listen

Translate article

Severe burn results in profound skeletal muscle atrophy; persistent muscle atrophy and weakness are major complications that hamper recovery from burn injury. Many factors contribute to the erosion of muscle mass following burn trauma, and we previously showed concurrent activation and apoptosis of muscle satellite cells (SC) following a burn injury in pediatric patients. To determine the necessity of satellite cells during muscle recovery following a burn injury, we utilized a genetically modified mouse model (Pax7‐DTA) that allows for the conditional depletion of satellite cells in skeletal muscle. Additionally, mice were provided 5‐ethynyl‐2′‐deoxyuridine (EdU) to determine satellite cell proliferation, activation and fusion. Juvenile SC‐wild type and SC‐depleted mice (8 weeks of age) were randomized to sham or burn injury, consisting of a dorsal scald burn injury covering 30% of total body surface area. Both hind‐limb and dorsal muscles were studied at 7, 14 and 21 days post‐burn. SC‐depleted mice had >93% fewer SC than SC‐wild type (P<0.05). Burn injury induced robust atrophy in muscles located both proximal and distal to the injury site (~30% decrease in fiber cross‐sectional area, P<0.05). Additionally, burn injury induced skeletal muscle regeneration, satellite cell proliferation and fusion. Depletion of satellite cells impaired post‐burn muscle recovery. These findings support an integral role for satellite cells in the etiology of lean tissue recovery following a severe burn injury.Support or Funding InformationThis project was supported by a pilot grant from the UTMB Department of Surgery and NIH grants P30 AG024832, P50 GM60338, R01 GM56687, R01 HD049471 and Shriners grants SHC 80480 and SHC 80500.