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Macrophage Depletion Impairs Skeletal Muscle Regeneration: the Roles of Pro-fibrotic Factors, Inflammation, and Oxidative Stress

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Abstract

Muscle contusion is one of the most common muscle injuries in sports medicine. Macrophages play complex roles in the regeneration of skeletal muscle. However, the roles of macrophages, especially the mechanisms involved, in the regeneration of muscle contusion are still not fully understood. We hypothesize that the depletion of macrophages impairs skeletal muscle regeneration and that pro-fibrotic factors, inflammation, and oxidative stress may be involved in the process. To test these hypotheses, we constructed a muscle contusion injury and a macrophage depletion model and followed it up with morphological and gene expression analyses. The data showed that fibrotic scars were formed in the muscle of contusion injury, and they deteriorated in the mice of macrophage depletion. Furthermore, the sizes of regenerating myofibers were significantly reduced by macrophage depletion. Pro-fibrotic factors, inflammatory cytokines, chemokines, and oxidative stress-related enzymes increased significantly after muscle injury. Moreover, the expression of these factors was delayed by macrophage depletion. Most of them were still significantly higher in the later stage of regeneration. These results suggest that macrophage depletion impairs skeletal muscle regeneration and that pro-fibrotic factors, inflammation, and oxidative stress may play important roles in the process.

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Abbreviations

GM:

Gastrocnemius muscle

CL-liposomes:

Clodronate-containing (CL) liposomes

HE staining:

Hematoxylin and eosin staining

PCR:

Polymerase chain reaction

TGF-beta 1:

Transforming growth factor-beta 1

TNF-alpha:

Tumor necrosis factor (TNF)-alpha

IL-1 beta:

Interleukin (IL)-1beta

IL-6:

Interleukin (IL)-6

IL-10:

Interleukin (IL)-10

CCL2:

CC ligand-2

CXCL10:

CXC ligand-10

NADPH-oxidases:

Nicotinamide adenine dinucleotide phosphate (NADPH)-oxidases

ROS:

Reactive oxygen species

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Acknowledgments

This work was supported by the grants from the National Natural Science Foundation of China (31271273, 31300975), the Doctoral Fund of Ministry of Education of China (20133156120004) and the Key Lab of Exercise and Health Sciences of Ministry of Education (Shanghai University of Sport).

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Authors and Affiliations

  1. School of Kinesiology, Shanghai University of Sport, Shanghai, 200438, China

    Weihua Xiao, Yu Liu & Peijie Chen

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  1. Weihua Xiao
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  2. Yu Liu
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  3. Peijie Chen
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Correspondence to Weihua Xiao or Peijie Chen.

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Authors’ Contributions

WX and PC analyzed and interpreted the data. YL performed the histological examination of the skeletal muscle. All authors read and approved the final manuscript.

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The authors declare that they have no conflict of interest.

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Xiao, W., Liu, Y. & Chen, P. Macrophage Depletion Impairs Skeletal Muscle Regeneration: the Roles of Pro-fibrotic Factors, Inflammation, and Oxidative Stress. Inflammation 39, 2016–2028 (2016). https://doi.org/10.1007/s10753-016-0438-8

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