Impaired Skeletal Muscle Regeneration Induced by Macrophage Depletion Could Be Partly Ameliorated by MGF Injection

Xiaoguang Liu,Peijie Chen,Linlin Zhao,Weihua Xiao,Zhigang Zeng

doi:10.3389/fphys.2019.00601

Xiaoguang Liu, Peijie Chen + Show 3 more

Open Access

https://doi.org/10.3389/fphys.2019.00601

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Abstract

Skeletal muscle injury is one of the most common injuries in sports medicine. Our previous study found that macrophage depletion impairs muscle regeneration and that mechano growth factor (MGF) may play an important role in this process. However, whether injection of MGF protects against impaired muscle regeneration after macrophage depletion has not been explored. Therefore, we generated a muscle contusion and macrophage depletion mouse model and injected MGF into the damaged muscle. Comprehensive morphological and genetic analyses were performed on the injured skeletal muscle after macrophage depletion and MGF injection. The results showed that injection of MGF did not exert a protective effect on muscle fiber regeneration; however, it did decrease fibrosis in the contused skeletal muscle after macrophage depletion. Moreover, MGF injection decreased the expression of muscle inflammatory cytokines (TNF-α, IFN-γ, IL-1β, and TGF-β), chemokines (CCL2, CCL5, and CXCR4), oxidative stress factors (gp91phox) and matrix metalloproteinases (MMP-1, MMP-2, MMP-9, MMP-10, and MMP-14). These results suggest that the impairment of skeletal muscle regeneration induced by macrophage depletion could be partly ameliorated by MGF injection and that inflammatory cytokines, oxidative stress factors, chemokines, and MMP may be involved in this process.

Highlights

Skeletal muscle accounts for almost half of the body weight in humans
RT-Polymerase Chain Reaction (PCR) results indicated that clodronate-containing liposomes significantly decreased the expression of the F4/80 macrophage marker at 1, 3, and 7 days (p < 0.01) post-skeletal muscle injury
These results suggest that mechano growth factor (MGF) injection improves skeletal muscle fibrosis after macrophage depletion but not by regulating the functional status of satellite cells

Summary

Introduction

Skeletal muscle accounts for almost half of the body weight in humans. As a power-generating tissue, it is one of the most important organs in mammals. Skeletal muscle injuries occur very often in humans and are inevitable. Skeletal muscle regeneration following an injury is a complicated process that involves many cells and cytokines (Tidball, 2011). Inflammation, especially macrophage inflammation, plays a crucial role in skeletal muscle regeneration (Kharraz et al, 2013). Experiments have revealed that skeletal muscle injury induces extensive macrophage infiltration at the injury site (Novak et al, 2014). There are two different phenotypes of macrophages, M1 and M2. Activated macrophages, typically designated M1 macrophages, are characterized by the expression of proinflammatory cytokines

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