Involvement of muscle stem cell in skeletal muscle hypertrophy induced by mechanical loading and drugs

Abstract

Skeletal muscle is the largest organ in our body, consisting of bundles of multinuclear cells called myofibers. Skeletal muscle is responsible for locomotion, metabolism, and life activities such as swallowing and respiration, and is also attracting attention as an endocrine organ. Skeletal muscle has two abilities, regeneration and adaptation, and the understanding of these mechanisms is expected to contribute to the development of therapies for muscle diseases such as muscular dystrophies and muscle atrophy. Skeletal muscle-specific stem cells, muscle satellite cells (MuSCs), are involved in these abilities. As well as other tissue stem cells, MuSCs are also maintained in a dormant state under steady-state conditions. However, when myofibers are damaged, they start to proliferate and eventually rebuilt new myofibers. While, muscle hypertrophy is one of the “adaptation”, and MuSCs contribute to muscle hypertrophy by supplying new nuclei to myofibers. In contrast to studies of MuSCs during regeneration, the dynamics of MuSCs during hypertrophy had not been well studied. One reason is that the specific regulatory mechanisms of MuSC in hypertrophic muscle had not been elucidated. In addition to physical stimuli, drugs such as dopings, hormones, and myostatin inhibition are known to induce muscle hypertrophy. The necessity of MuSCs and new myonuclei in various model of muscle hypertrophy has been highly debated. In this review, we introduce the mechanism of MuSC proliferation specific to hypertrophic muscle, and outline the mechanism of muscle hypertrophy induced by exercise and drugs and the involvement of MuSCs.