Reduced voluntary running performance is associated with impaired coordination as a result of muscle satellite cell depletion in adult mice

Satellite cells, or muscle stem cells, have been thought to be responsible for all muscle plasticity, but recent studies using genetically modified mouse models that allow for the conditional ablation of satellite cells have challenged this dogma.

Depletion of Pax7-expressing cells in muscle resulted in reduced voluntary wheel running performance, without affecting markers of aerobic adaptation; however, their absence may perturb proprioception via disruption of muscle spindle fibers resulting in loss of gross motor coordination, indicating that satellite cells have a yet unexplored role in muscle function.

Four-month-old female Pax7/DTA mice (n = 8-12 per group) were satellite cell depleted via tamoxifen administration; at 6 months of age, mice either remained sedentary or were provided with running wheels for 8 weeks. Plantaris muscles were significantly depleted of Pax7+cells (≥90 % depleted), and 8 weeks of wheel running did not result in an increase in Pax7+ cells, or in myonuclear accretion. Interestingly, satellite cell-depleted animals ran ~27 % less distance and were 23 % slower than non-depleted animals. Wheel running was associated with elevated succinate dehydrogenase activity, muscle vascularization, lipid accumulation, and a significant shift toward more oxidative myosin heavy chain isoforms, as well as an increase in voltage dependent anion channel abundance, a marker of mitochondrial density. Importantly, these changes were independent of satellite cell content. Interestingly, depletion of Pax7+ cells from intra- as well as extrafusal muscle fibers resulted in atrophy of intrafusal fibers, thickening of muscle spindle-associated extracellular matrix, and a marked reduction of functional outcomes including grip strength, gait fluidity, and balance, which likely contributed to the impaired running performance. Conclusions: Depletion of Pax7-expressing cells in muscle resulted in reduced voluntary wheel running performance, without affecting markers of aerobic adaptation; however, their absence may perturb proprioception via disruption of muscle spindle fibers resulting in loss of gross motor coordination, indicating that satellite cells have a yet unexplored role in muscle function.