Role of satellite cells in skeletal muscle plasticity: Beyond muscle regeneration

Abstract Duchenne muscular dystrophy (DMD) is a progressive disease characterised by chronic muscle degeneration and inflammation. Our previously established DMD model rats (DMD rats) have a more severe disease phenotype than the broadly used mouse model. We aimed to investigate the role of senescence in DMD using DMD rats and patients. Senescence was induced in satellite cells and mesenchymal progenitor cells, owing to the increased expression of CDKN2A, p16- and p19-encoding gene. Genetic ablation of p16 in DMD rats dramatically restored body weight and muscle strength. Histological analysis showed a reduction of fibrotic and adipose tissues invading skeletal muscle, with increased muscle regeneration. Senolytic drug ABT263 prevented loss of body weight and muscle strength, and increased muscle regeneration in rats even at 8 months—the late stage of DMD. Moreover, senescence markers were highly expressed in the skeletal muscle of DMD patients. In situ hybridization of CDKN2A confirmed the expression of it in satellite cells and mesenchymal progenitor cells in patients with DMD. Collectively, these data provide new insights into the integral role of senescence in DMD progression.

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Satellite cells and skeletal muscle regeneration

British Journal of Surgery ◽

10.1002/bjs.1800530720 ◽

1966 ◽

Vol 53 (7) ◽

pp. 638-642 ◽

Cited By ~ 66

Author(s):

J. C. T. Church ◽

R. F. X. Noronha ◽

D. B. Allbrook

Keyword(s):

Skeletal Muscle ◽

Satellite Cells ◽

Muscle Regeneration ◽

Skeletal Muscle Regeneration

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The LIM domain protein nTRIP6 modulates the dynamics of myogenic differentiation

Scientific Reports ◽

10.1038/s41598-021-92331-8 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Tannaz Norizadeh Abbariki ◽

Zita Gonda ◽

Denise Kemler ◽

Pavel Urbanek ◽

Tabea Wagner ◽

...

Keyword(s):

Skeletal Muscle ◽

Satellite Cells ◽

Muscle Regeneration ◽

Myogenic Differentiation ◽

Skeletal Muscle Regeneration ◽

Temporal Control ◽

Lim Domain ◽

Lim Domain Protein ◽

Domain Protein

AbstractThe process of myogenesis which operates during skeletal muscle regeneration involves the activation of muscle stem cells, the so-called satellite cells. These then give rise to proliferating progenitors, the myoblasts which subsequently exit the cell cycle and differentiate into committed precursors, the myocytes. Ultimately, the fusion of myocytes leads to myofiber formation. Here we reveal a role for the transcriptional co-regulator nTRIP6, the nuclear isoform of the LIM-domain protein TRIP6, in the temporal control of myogenesis. In an in vitro model of myogenesis, the expression of nTRIP6 is transiently up-regulated at the transition between proliferation and differentiation, whereas that of the cytosolic isoform TRIP6 is not altered. Selectively blocking nTRIP6 function results in accelerated early differentiation followed by deregulated late differentiation and fusion. Thus, the transient increase in nTRIP6 expression appears to prevent premature differentiation. Accordingly, knocking out the Trip6 gene in satellite cells leads to deregulated skeletal muscle regeneration dynamics in the mouse. Thus, dynamic changes in nTRIP6 expression contributes to the temporal control of myogenesis.

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The Role of Metabolic Remodeling in Macrophage Polarization and Its Effect on Skeletal Muscle Regeneration

Antioxidants and Redox Signaling ◽

10.1089/ars.2017.7420 ◽

2019 ◽

Vol 30 (12) ◽

pp. 1553-1598 ◽

Cited By ~ 10

Author(s):

Francesca De Santa ◽

Laura Vitiello ◽

Alessio Torcinaro ◽

Elisabetta Ferraro

Keyword(s):

Skeletal Muscle ◽

Muscle Regeneration ◽

Macrophage Polarization ◽

Skeletal Muscle Regeneration ◽

Metabolic Remodeling

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Satellite cells in human skeletal muscle plasticity

Frontiers in Physiology ◽

10.3389/fphys.2015.00283 ◽

2015 ◽

Vol 6 ◽

Cited By ~ 107

Author(s):

Tim Snijders ◽

Joshua P. Nederveen ◽

Bryon R. McKay ◽

Sophie Joanisse ◽

Lex B. Verdijk ◽

...

Keyword(s):

Skeletal Muscle ◽

Satellite Cells ◽

Human Skeletal Muscle ◽

Muscle Plasticity

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Acid Sphingomyelinase Controls Early Phases of Skeletal Muscle Regeneration by Shaping the Macrophage Phenotype

Cells ◽

10.3390/cells10113028 ◽

2021 ◽

Vol 10 (11) ◽

pp. 3028

Author(s):

Paulina Roux-Biejat ◽

Marco Coazzoli ◽

Pasquale Marrazzo ◽

Silvia Zecchini ◽

Ilaria Di Renzo ◽

...

Keyword(s):

Skeletal Muscle ◽

Satellite Cells ◽

Muscle Regeneration ◽

Acid Sphingomyelinase ◽

Skeletal Muscle Regeneration ◽

Sphingolipid Metabolism ◽

M2 Macrophages ◽

Macrophage Phenotype ◽

M1 Macrophages ◽

Early Phases

Skeletal muscle regeneration is a complex process involving crosstalk between immune cells and myogenic precursor cells, i.e., satellite cells. In this scenario, macrophage recruitment in damaged muscles is a mandatory step for tissue repair since pro-inflammatory M1 macrophages promote the activation of satellite cells, stimulating their proliferation and then, after switching into anti-inflammatory M2 macrophages, they prompt satellite cells’ differentiation into myotubes and resolve inflammation. Here, we show that acid sphingomyelinase (ASMase), a key enzyme in sphingolipid metabolism, is activated after skeletal muscle injury induced in vivo by the injection of cardiotoxin. ASMase ablation shortens the early phases of skeletal muscle regeneration without affecting satellite cell behavior. Of interest, ASMase regulates the balance between M1 and M2 macrophages in the injured muscles so that the absence of the enzyme reduces inflammation. The analysis of macrophage populations indicates that these events depend on the altered polarization of M1 macrophages towards an M2 phenotype. Our results unravel a novel role of ASMase in regulating immune response during muscle regeneration/repair and suggest ASMase as a supplemental therapeutic target in conditions of redundant inflammation that impairs muscle recovery.

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The IRE1/XBP1 signaling axis promotes skeletal muscle regeneration through a cell non-autonomous mechanism

eLife ◽

10.7554/elife.73215 ◽

2021 ◽

Vol 10 ◽

Author(s):

Anirban Roy ◽

Meiricris Tomaz da Silva ◽

Raksha Bhat ◽

Kyle R Bohnert ◽

Takao Iwawaki ◽

...

Keyword(s):

Skeletal Muscle ◽

Satellite Cells ◽

Muscle Regeneration ◽

Ex Vivo ◽

Skeletal Muscle Regeneration ◽

Mdx Mice ◽

Major Mechanism ◽

Downstream Target ◽

A Cell ◽

The Unfolded Protein Response

Skeletal muscle regeneration is regulated by coordinated activation of multiple signaling pathways activated in both injured myofibers and satellite cells. The unfolded protein response (UPR) is a major mechanism that detects and alleviates protein-folding stresses in ER. However, the role of individual arms of the UPR in skeletal muscle regeneration remain less understood. In the present study, we demonstrate that IRE1α (also known as ERN1) and its downstream target, XBP1, are activated in skeletal muscle of mice upon injury. Myofiber-specific ablation of IRE1 or XBP1 in mice diminishes skeletal muscle regeneration that is accompanied with reduced number of satellite cells and their fusion to injured myofibers. Ex vivo cultures of myofiber explants demonstrate that ablation of IRE1α reduces the proliferative capacity of myofiber-associated satellite cells. Myofiber-specific deletion of IRE1α dampens Notch signaling and canonical NF-kB pathway in skeletal muscle of mice. Our results also demonstrate that targeted ablation of IRE1α reduces skeletal muscle regeneration in the mdx mice, a model of Duchenne muscular dystrophy. Collectively, our results reveal that the IRE1α-mediated signaling promotes muscle regeneration through augmenting the proliferation of satellite cells in a cell non-autonomous manner.

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The Potential Role of Insulin-Like Growth Factors in Skeletal Muscle Regeneration

Canadian Journal of Applied Physiology ◽

10.1139/h96-021 ◽

1996 ◽

Vol 21 (4) ◽

pp. 236-250 ◽

Cited By ~ 19

Author(s):

Jamie MacGregor ◽

Wade S. Parkhouse

Keyword(s):

Skeletal Muscle ◽

Growth Hormone ◽

Growth Factors ◽

Muscle Regeneration ◽

Potential Role ◽

Tissue Growth ◽

Skeletal Muscle Regeneration ◽

Tissue Type ◽

Insulin Like Growth Factors

The role of the insulin-like growth factors I and II (IGF-I and IGF-II), previously known as the somatomedins, in general growth and development of various tissues has been known for many years. Thought of exclusively as endocrine factors produced by the liver, and under the control of growth hormone, the somatomedins were known as the intermediaries by which growth hormone exerted its cellular effects during tissue growth and maturation. Eventually it was discovered that virtually every tissue type is capable of autocrine production of the IGFs, and their involvement in skeletal muscle tissue repair and regeneration became apparent. Recent advances in technology have allowed the characterisation of many of the different growth factors believed to play a role in muscle regeneration, and experimental manipulations of cells in culture have provided insight into the effects of the various growth factors on the myoblast. This paper explores the potential role of the IGFs in skeletal muscle regeneration. A critical role of IGF-II in terminal differentiation of proliferating muscle precurser cells following injury is proposed. Key words: growth factors, myogenesis, skeletal muscle regeneration

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MiR-27b Promotes Muscle Development by Inhibiting MDFI Expression

Cellular Physiology and Biochemistry ◽

10.1159/000489595 ◽

2018 ◽

Vol 46 (6) ◽

pp. 2271-2283 ◽

Cited By ~ 12

Author(s):

Lianjie Hou ◽

Jian Xu ◽

Yiren Jiao ◽

Huaqin Li ◽

Zhicheng Pan ◽

...

Keyword(s):

Skeletal Muscle ◽

Western Blot ◽

Satellite Cells ◽

Muscle Regeneration ◽

Muscle Injury ◽

Target Gene ◽

Muscle Development ◽

Muscle Satellite Cells ◽

Qrt Pcr

Background/Aims: Skeletal muscle plays an essential role in the body movement. However, injuries to the skeletal muscle are common. Lifelong maintenance of skeletal muscle function largely depends on preserving the regenerative capacity of muscle. Muscle satellite cells proliferation, differentiation, and myoblast fusion play an important role in muscle regeneration after injury. Therefore, understanding of the mechanisms associated with muscle development during muscle regeneration is essential for devising the alternative treatments for muscle injury in the future. Methods: Edu staining, qRT-PCR and western blot were used to evaluate the miR-27b effects on pig muscle satellite cells (PSCs) proliferation and differentiation in vitro. Then, we used bioinformatics analysis and dual-luciferase reporter assay to predict and confirm the miR-27b target gene. Finally, we elucidate the target gene function on muscle development in vitro and in vivo through Edu staining, qRT-PCR, western blot, H&E staining and morphological observation. Result: miR-27b inhibits PSCs proliferation and promotes PSCs differentiation. And the miR-27b target gene, MDFI, promotes PSCs proliferation and inhibits PSCs differentiation in vitro. Furthermore, interfering MDFI expression promotes mice muscle regeneration after injury. Conclusion: our results conclude that miR-27b promotes PSCs myogenesis by targeting MDFI. These results expand our understanding of muscle development mechanism in which miRNAs and genes work collaboratively in regulating skeletal muscle development. Furthermore, this finding has implications for obtaining the alternative treatments for patients with the muscle injury.

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