Abstract

Muscle regeneration is a closely regulated process that involves a variety of cell types such as satellite cells, myofibers, fibroadipogenic progenitors, endothelial cells, and inflammatory cells. Among these different cell types, macrophages emerged as a central actor coordinating the different cellular interactions and biological processes. Particularly, the transition of macrophages from their proinflammatory to their anti-inflammatory phenotype was shown to regulate inflammation, myogenesis, fibrosis, vascularization, and return to homeostasis. On the other hand, deregulation of macrophage accumulation or polarization in chronic degenerative muscle disorders was shown to impair muscle regeneration. Considering the key roles of macrophages in skeletal muscle, they represent an attractive target for new therapeutic approaches aiming at mitigating various muscle disorders. This review aims at summarizing the novel insights into macrophage heterogeneity, plasticity, and functions in skeletal muscle homeostasis, regeneration, and disease.

Highlights

  • Skeletal muscle injury can be caused by a variety of conditions such as direct trauma, disuse, ischemia, exercise, toxins, and genetic diseases

  • There are numerous evidences indicating that macrophages are key regulators of different biological processes involved during skeletal muscle regeneration, such as myogenesis, fibrosis, inflammation, and revascularization [3,4,5,6,7,8,9]

  • Muscle regeneration relies on different stem cell types, especially satellite cells and fibroadipogenic progenitors (FAPs)

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Summary

Introduction

Skeletal muscle injury can be caused by a variety of conditions such as direct trauma, disuse, ischemia, exercise, toxins, and genetic diseases. To face these challenges, skeletal muscle has developed a remarkable regenerative capacity, which relies on muscle stem cells, named satellite cells. There are numerous evidences indicating that macrophages are key regulators of different biological processes involved during skeletal muscle regeneration, such as myogenesis, fibrosis, inflammation, and revascularization [3,4,5,6,7,8,9]. This review will discuss these novel insights into the role of macrophages in muscle homeostasis, regeneration, and diseases with a particular focus on Duchenne muscular dystrophy (DMD). Promising strategies targeting macrophage polarization in physiopathological conditions will be discussed

Origin and Recruitment of Monocyte and Macrophages
Macrophage Subsets and Polarization
Macrophages in Chronic Muscle Disorders
Macrophages in Muscle Aging
Promoting Muscle Regeneration by Modulating the Macrophage Phenotype
Anti-Inflammatory Cytokines and Growth Factors
RNA Silencing
Nutritional Compounds
Conclusion
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