Ablation of Satellite Cell-specific Clock Gene, Bmal1, Alters Force Production, Muscle Damage, and Repair Following Contractile-induced Injury

Overview

Journal FASEB J

Date 2025 Jan 15

PMID 39812604

Authors

Ryan E Kahn

Pei Zhu

Ishan Roy

Clara Peek

John A Hawley

Sudarshan Dayanidhi

Affiliations

Soon will be listed here.

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-Bmal1 animals exhibited a ~20-25% reduction in normalized force production (ex vivo and in vivo) versus control SC-Bmal1 and SC-Bmal1 untreated littermates (p < .05). Following contractile injury, SC-Bmal1 animals displayed reduced muscle damage and subsequent repair post-injury (Dystrophin fibers 24 h: SC-Bmal1 199 ± 41; SC-Bmal1 36 ± 13, p < .05) (eMHC fibers 7 day: SC-Bmal1 217.8 ± 115.5; SC-Bmal1 27.8 ± 17.3; Centralized nuclei 7 day: SC-Bmal1 160.7 ± 70.5; SC-Bmal1 46.2 ± 15.7). SC-Bmal1 animals also showed reduced neutrophil infiltration, consistent with less injury (Neutrophil content 24 h: SC-Bmal1 2.4 ± 0.4; SC-Bmal1 0.4 ± 0.2, % area fraction, p < .05). SC-Bmal1 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.

Citing Articles

Ablation of satellite cell-specific clock gene, Bmal1, alters force production, muscle damage, and repair following contractile-induced injury.

Kahn R, Zhu P, Roy I, Peek C, Hawley J, Dayanidhi S FASEB J. 2025; 39(2):e70325.

PMID: 39812604 PMC: 11734708. DOI: 10.1096/fj.202402145RR.

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