Mild Hyperthermia-Induced Myogenic Differentiation in Skeletal Muscle Cells: Implications for Local Hyperthermic Therapy for Skeletal Muscle Injury.

Hojun Lee,Seung-Jun Choi

doi:10.1155/2018/2393570

Abstract

The percutaneous application of controlled temperature on damaged muscle is regarded as a prevalent remedy. However, specific mechanisms are not completely understood. Therefore, cellular behaviors of myoblasts were investigated under a physiological hyperthermic temperature. The myoblasts were cultured under no treatment (NT, 37°C, 24 h/day), intermittent heat treatment (IHT, 39°C, 2 h/day), and continuous heat treatment (CHT, 39°C, 24 h/day) during proliferation, migration, or myogenic differentiation. Although the effects of mild heat on migration were not observed, the proliferation was promoted by both IHT and CHT. The myogenic differentiation was also enhanced in a treatment time-dependent manner, as evidenced by an increase in myotube size and fusion index. The gene expressions of mitochondrial biogenesis (Pgc-1α, Nrf1, and Tfam), a subset of mitochondrial dynamics (Mfn1 and Drp1), and a myogenic regulatory factor (myogenin) were increased in a heat treatment time-dependent manner. Interestingly, the mild heat-induced myogenic differentiation and myogenin expression were retarded significantly in PGC-1α-targeted siRNA-transfected cells, suggesting that mild hyperthermia promotes myogenic differentiation via the modulation of PGC-1α. This study provides cellular evidence supporting that local hyperthermic treatment at 39°C is regarded as an effective therapeutic strategy to promote satellite cell activities in regenerating myofibers.

Highlights

Recovery from skeletal muscle injury is orchestrated by a series of events consisting of degeneration, inflammation, and regeneration [1]
Several lines of studies proved that the application of mild heat treatment at 39°C is conducive to myogenesis while temperature at 41°C is detrimental to satellite cell activities [10, 11], providing a piece of evidence that the intrinsic biological capacity of satellite cell is tightly modulated in a temperature-sensitive manner
The total myonuclei number was lower in the chronic heat treatment (CHT) group compared to the IHT and NT groups (Figure 2(d)) while the myotube fusion index was greatest in the CHT group (p < 0 05, Figure 2(e)), indicating that more myoblasts were involved in myogenic differentiation

Summary

Introduction

Recovery from skeletal muscle injury is orchestrated by a series of events consisting of degeneration, inflammation, and regeneration [1]. Macrophages matured from monocytes remove damaged cells by phagocytosis but produce chemotactic signaling molecules leading to the activation of satellite cells for the proper regeneration of injured myofibers [3]. A study suggested that skeletal muscle regeneration is attenuated by hypothemic therapy due to the excessive suppression of inflammatory reactions, suggesting that a proper inflammatory process in the initial phase of recovery is critical for the facilitated regeneration of myofibers [9]. Heat treatment has been demonstrated to increase macrophage activation, leading to an increase in Oxidative Medicine and Cellular Longevity the number of regenerating muscle fibers in the damaged extensor digitorum longus of experimental rats [4]. Several lines of studies proved that the application of mild heat treatment at 39°C is conducive to myogenesis while temperature at 41°C is detrimental to satellite cell activities [10, 11], providing a piece of evidence that the intrinsic biological capacity of satellite cell is tightly modulated in a temperature-sensitive manner

Methods

Results

Conclusion