Muscle Stem Cell Depletion Blunts Skeletal Muscle Adaptation to Weighted Wheel Running

Abstract

Satellite cells, the resident muscle stem cell, are not required for short term skeletal muscle hypertrophy in mice when subjected to mechanical overload via synergist ablation, however, long term growth is blunted. This study aimed to further investigate the effect of satellite cell depletion on muscle adaptation using Progressive Weighted Wheel Running (PoWeR). We hypothesized that satellite cell depletion would reduce the adaptive response of skeletal muscle to the training stimulus. The Pax7‐DTA mouse model was used to deplete satellite cell content in adult skeletal muscle. PoWeR training involved adding weight to the running wheel of the mice incrementally over the 8‐week training period. Hindlimb muscles were excised at the 8‐week time point, and the plantaris was immunohistochemically analyzed. PoWeR induced an oxidative shift in fiber type distribution and increased muscle fiber cross sectional area (CSA). However, this increase in fiber CSA was blunted in mice without satellite cells. To investigate the blunted growth in satellite cell‐depleted mice, the plantaris was analyzed for extracellular matrix content and capillarization. We found that neither extracellular matrix buildup nor capillary density differed between satellite cell replete and depleted groups following PoWeR. These findings suggest that loss of satellite cells reduces the capacity for hypertrophy in response to PoWeR, but this was not due to excessive extracellular matrix accumulation. Further, satellite cells were not required for a robust fiber type shift in response to PoWeR training.Support or Funding InformationThis work was funded by the American Physiological Society’s UGSRF program and a grant from the National Institute of Health to Dr. Charlotte Peterson and Dr. John McCarthy (AR060701).