Abstract
Following injury, skeletal muscle undergoes repair via satellite cell (SC)-mediated myogenic progression. In SCs, the circadian molecular clock gene, Bmal1, is necessary for appropriate myogenic progression and repair with evidence that muscle molecular clocks can also affect force production. Utilizing a mouse model allowing for inducible depletion of Bmal1 within SCs, we determined contractile function, SC myogenic progression and muscle damage and repair following eccentric contractile-induced injury. At baseline, SC-Bmal1iKO animals exhibited a ~20-25% reduction in normalized force production (ex vivo and in vivo) versus control SC-Bmal1Cntrl and SC-Bmal1iKO untreated littermates (p < .05). Following contractile injury, SC-Bmal1iKO animals displayed reduced muscle damage and subsequent repair post-injury (Dystrophinnegative fibers 24 h: SC-Bmal1Cntrl 199 ± 41; SC-Bmal1iKO 36 ± 13, p < .05) (eMHC+ fibers 7 day: SC-Bmal1Cntrl 217.8 ± 115.5; SC-Bmal1iKO 27.8 ± 17.3; Centralized nuclei 7 day: SC-Bmal1Cntrl 160.7 ± 70.5; SC-Bmal1iKO 46.2 ± 15.7). SC-Bmal1iKO animals also showed reduced neutrophil infiltration, consistent with less injury (Neutrophil content 24 h: SC-Bmal1Cntrl 2.4 ± 0.4; SC-Bmal1iKO 0.4 ± 0.2, % area fraction, p < .05). SC-Bmal1iKO animals had greater SC activation/proliferation at an earlier timepoint (p < .05) and an unexplained increase in activation 7 days post injury. Collectively, these data suggest SC-Bmal1 plays a regulatory role in force production, influencing the magnitude of muscle damage/repair, with an altered SC myogenic progression following contractile-induced muscle injury.