Satellite Cell Depletion Negatively Impacts Voluntary Wheel Running Performance in Mice

Abstract

Satellite cells have long been thought to be responsible for muscle plasticity. Recent studies in the field using genetically‐modified mouse models that allow for conditional satellite cell ablation have challenged this dogma. Although these studies confirmed that satellite cells are required for muscle regeneration, they surprisingly show that they are not required for muscle growth. While the role that muscle stem cells play in muscle growth and regeneration are being defined, their role in muscle response to aerobic exercise remains unexplored. Therefore the purpose of the current study is to assess the involvement of satellite cells in response to voluntary wheel running. Female Pax7‐DTA mice were satellite cell depleted following tamoxifen administration. Mice were either ambulatory, or were wheel run for 8 weeks. Satellite cell depleted animals ran ~38% less km/day and 23% slower than non‐depleted animals. Succinate dehydrogenase was significantly elevated in plantaris muscles with running, but staining intensity tended to be attenuated in satellite cell‐depleted muscle. Myosin heavy chain isoforms were significantly altered with running, independent of satellite cell ablation. Similarly, fiber vascularization, quantified using the endothelial marker CD31, was elevated with running, but was unaffected by satellite cell depletion. In conclusion, the presence of satellite cells appears to be beneficial to voluntary running performance. The metabolic processes that may be altered in the absence of satellite cells that contribute to decreased endurance are currently under investigation. Funding: NIAMS R01AR060701