Efficacy of passive repetitive stretching of skeletal muscle on myofiber hypertrophy and genetic suppression on MAFbx, MuRF1, and myostatin.

Skeletal muscles undergo adaptations in response to mechanical stimuli such as stretching. However, there is limited evidence regarding the hypertrophic effects of passive repetitive stretching in vivo. We examined the effect of passive repetitive stretching on skeletal muscle myofiber morphology, satellite cell content, and messenger RNA expression of myogenic regulatory factors and signaling molecules involved in muscle protein synthesis and degradation. The gastrocnemius muscles of mice were stretched 15 times/min by manual ankle dorsiflexion for 15 min, 5 days a week for 2 weeks. We found that passive repetitive stretching significantly increased myofiber cross-sectional area. In stretched gastrocnemius muscles, the messenger RNA expression of p70S6K and myogenin was upregulated, whereas MuRF1, MAFbx, myostatin, and 4E-BP1 were downregulated. The phosphorylation level of p70S6K was significantly increased in stretched muscles. The number of Pax7+ cells was unaffected. Passive repetitive stretching induces muscle hypertrophy by regulating signaling pathways involved in muscle protein turnover. These findings are applicable to clinical muscle strengthening and for the maintenance of skeletal muscle mass and function in patients who are unconscious or paralyzed.