scholarly journals Importance of Nutrient Availability and Metabolism for Skeletal Muscle Regeneration

2021 ◽  
Vol 12 ◽  
Author(s):  
Jamie Blum ◽  
Rebekah Epstein ◽  
Stephen Watts ◽  
Anna Thalacker-Mercer
Keyword(s):  
Quality Of Life ◽  
Skeletal Muscle ◽  
Muscle Regeneration ◽  
Progenitor Cell ◽  
Cell Function ◽  
Functional Decline ◽  
Skeletal Muscle Regeneration ◽  
Skeletal Muscle Damage ◽  
Muscle Health

Skeletal muscle is fundamentally important for quality of life. Deterioration of skeletal muscle, such as that observed with advancing age, chronic disease, and dystrophies, is associated with metabolic and functional decline. Muscle stem/progenitor cells promote the maintenance of skeletal muscle composition (balance of muscle mass, fat, and fibrotic tissues) and are essential for the regenerative response to skeletal muscle damage. It is increasing recognized that nutrient and metabolic determinants of stem/progenitor cell function exist and are potential therapeutic targets to improve regenerative outcomes and muscle health. This review will focus on current understanding as well as key gaps in knowledge and challenges around identifying and understanding nutrient and metabolic determinants of skeletal muscle regeneration.

scholarly journals Immunoneutralization of TGFβ1 Improves Skeletal Muscle Regeneration: Effects on Myoblast Differentiation and Glycosaminoglycan Content

2009 ◽  
Vol 2009 ◽  
pp. 1-16 ◽  
Author(s):  
M. Zimowska ◽  
A. Duchesnay ◽  
P. Dragun ◽  
A. Oberbek ◽  
J. Moraczewski ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Muscle Regeneration ◽  
Skeletal Muscle Regeneration ◽  
Myoblast Differentiation ◽  
In Vitro Growth ◽  
Muscle Repair ◽  
Slow Twitch ◽  
Fast Twitch

When injured by crushing, the repair of the slow-twitch soleus rat muscle, unlike the fast-twitch EDL, is associated with fibrosis. As TGFβ1, whose activity can be controlled by glycosaminoglycans (GAG), plays a major role in fibrosis, we hypothesized that levels of TGFβ1 and GAG contents could account for this differential quality of regeneration. Here we show that the regeneration of the soleus was accompanied by elevated and more sustained TGFβ1 level than in the EDL. Neutralization of TGFβ1 effects by antibodies to TGFβ1 or its receptor TGFβ-R1 improved muscle repair, especially of the soleus muscle, increased in vitro growth of myoblasts, and accelerated their differentiation. These processes were accompanied by alterations of GAG contents. These results indicate that the control of TGFβ1 activity is important to improve regeneration of injured muscle and accelerate myoblast differentiation, in part through changes in GAG composition of muscle cell environment.

p21 is essential for normal myogenic progenitor cell function in regenerating skeletal muscle

2003 ◽  
Vol 285 (5) ◽  
pp. C1019-C1027 ◽  
Author(s):  
T. J. Hawke ◽  
A. P. Meeson ◽  
N. Jiang ◽  
S. Graham ◽  
K. Hutcheson ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Skeletal Muscle ◽  
Muscle Regeneration ◽  
Cell Function ◽  
Kinase Inhibitor ◽  
Cell Number ◽  
Skeletal Muscle Regeneration ◽  
Wild Type ◽  
Compensatory Mechanisms ◽  
Myogenic Progenitor

Despite the ability of myogenic progenitor cells (MPCs) to completely regenerate skeletal muscle following injury, little is known regarding the molecular program that regulates their proliferation and differentiation. Although mice lacking the cyclin-dependent kinase inhibitor p21 (p21-/-), develop normally, we report here that p21-/- MPCs display increased cell number and enhanced cell cycle progression compared with wild-type MPCs. Therefore, we hypothesized that p21-/- mice would demonstrate temporally enhanced regeneration following myotrauma. In response to cardiotoxin-induced injury, p21-/- skeletal muscle regeneration was significantly attenuated vs. regenerating wild-type muscle, contrary to the hypothesis. Regenerating p21-/- skeletal muscle displayed increased proliferative (PCNA positive) nuclei coincident with increased apoptotic nuclei (TUNEL positive) compared with wild-type muscle up to 3 wk after injury. Differentiation of p21-/- MPCs was markedly impaired and associated with increased apoptosis compared with wild-type MPCs, confirming that the impaired differentiation of the p21-/- MPCs was a cell autonomous event. No dysregulation of p27, p53, or p57 protein expression in differentiating p21-/- MPCs compared with wild-type MPCs was observed, suggesting that other compensatory mechanisms are responsible for the regeneration that ultimately occurs. On the basis of these findings, we propose that p21 is essential for the coordination of cell cycle exit and differentiation in the adult MPC population and that in the absence of p21, skeletal muscle regeneration is markedly impaired.

Rad is temporally regulated within myogenic progenitor cells during skeletal muscle regeneration

2006 ◽  
Vol 290 (2) ◽  
pp. C379-C387 ◽  
Author(s):  
Thomas J. Hawke ◽  
Shane B. Kanatous ◽  
Cindy M. Martin ◽  
Sean C. Goetsch ◽  
Daniel J. Garry
Keyword(s):  
Skeletal Muscle ◽  
Progenitor Cells ◽  
Cell Population ◽  
Muscle Regeneration ◽  
Progenitor Cell ◽  
Transcriptional Activity ◽  
Skeletal Muscle Regeneration ◽  
Progenitor Cell Population ◽  
Myogenic Progenitor Cells ◽  
Myogenic Progenitor

The successful use of myogenic progenitor cells for therapeutic applications requires an understanding of the intrinsic and extrinsic cues involved in their regulation. Herein we demonstrate the expression pattern and transcriptional regulation of Rad, a prototypical member of a family of novel Ras-related GTPases, during mammalian development and skeletal muscle regeneration. Rad was identified using microarray analysis, which revealed robust upregulation of its expression during skeletal muscle regeneration. Our current findings demonstrate negligible Rad expression with resting adult skeletal muscle; however, after muscle injury, Rad is expressed within the myogenic progenitor cell population. Rad expression is significantly increased and localized to the myogenic progenitor cell population during the early phases of regeneration and within the newly regenerated myofibers during the later phases of regeneration. Immunohistochemical analysis demonstrated that Rad and MyoD are coexpressed within the myogenic progenitor cell population of regenerating skeletal muscle. This expression profile of Rad during skeletal muscle regeneration is consistent with the proposed roles for Rad in the inhibition of L-type Ca2+channel activity and the inhibition of Rho/RhoA kinase activity. We also have demonstrated that known myogenic transcription factors (MEF2, MyoD, and Myf-5) can increase the transcriptional activity of the Rad promoter and that this ability is significantly enhanced by the presence of the Ca2+-dependent phosphatase calcineurin. Furthermore, this enhanced transcriptional activity appears to be dependent on the presence of a conserved NFAT binding motif within the Rad promoter. Taken together, these data define Rad as a novel factor within the myogenic progenitor cells of skeletal muscle and identify key regulators of its transcriptional activity.

scholarly journals Canonical NF-κB signaling regulates satellite stem cell homeostasis and function during regenerative myogenesis

2018 ◽  
Vol 11 (1) ◽  
pp. 53-66 ◽  
Author(s):  
Alex R Straughn ◽  
Sajedah M Hindi ◽  
Guangyan Xiong ◽  
Ashok Kumar
Keyword(s):  
Skeletal Muscle ◽  
Satellite Cell ◽  
Satellite Cells ◽  
Muscle Regeneration ◽  
Cell Function ◽  
Skeletal Muscle Regeneration ◽  
Cell Homeostasis ◽  
Adult Skeletal Muscle ◽  
Adult Mice ◽  
And Function

Abstract Skeletal muscle regeneration in adults is attributed to the presence of satellite stem cells that proliferate, differentiate, and eventually fuse with injured myofibers. However, the signaling mechanisms that regulate satellite cell homeostasis and function remain less understood. While IKKβ-mediated canonical NF-κB signaling has been implicated in the regulation of myogenesis and skeletal muscle mass, its role in the regulation of satellite cell function during muscle regeneration has not been fully elucidated. Here, we report that canonical NF-κB signaling is induced in skeletal muscle upon injury. Satellite cell-specific inducible ablation of IKKβ attenuates skeletal muscle regeneration in adult mice. Targeted ablation of IKKβ also reduces the number of satellite cells in injured skeletal muscle of adult mice, potentially through inhibiting their proliferation and survival. We also demonstrate that the inhibition of specific components of the canonical NF-κB pathway causes precocious differentiation of cultured satellite cells both ex vivo and in vitro. Finally, our results highlight that the constitutive activation of canonical NF-κB signaling in satellite cells also attenuates skeletal muscle regeneration following injury in adult mice. Collectively, our study demonstrates that the proper regulation of canonical NF-κB signaling is important for the regeneration of adult skeletal muscle.

scholarly journals The mechanosensitive Ca2+-permeable ion channel PIEZO1 promotes satellite cell function in skeletal muscle regeneration

2021 ◽  
Author(s):  
Kotaro Hirano ◽  
Masaki Tsuchiya ◽  
Seiji Takabayashi ◽  
Kohjiro Nagao ◽  
Yasuo Kitajima ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Ion Channel ◽  
Muscle Regeneration ◽  
Cell Function ◽  
Skeletal Muscle Regeneration ◽  
Growth Defect ◽  
Mechanical Stimuli ◽  
Conditional Deletion ◽  
Myogenic Stem Cells ◽  
And Function

AbstractMuscle satellite cells (MuSCs), myogenic stem cells in skeletal muscle, play an essential role in muscle regeneration. During the regeneration process, cues from the surrounding microenvironment are critical for the proliferation and function of MuSCs. However, the mechanism by which mechanical stimuli from the MuSCs niche is converted into biochemical signals to promote muscle regeneration is yet to be determined. Here, we show that PIEZO1, a calcium ion (Ca2+)-permeable cation channel that is activated by membrane tension, mediates the spontaneous Ca2+ influx to controls the regenerative function of MuSCs. Our genetically engineering approach in mice revealed that PIEZO1 is functionally expressed in MuSCs, and the conditional deletion of Piezo1 in MuSCs delays myofiber regeneration after myofiber injury, which is at least in part due to the growth defect in MuSCs via the reduction in RhoA-mediated actomyosin formation. Thus, we provide the first evidence in MuSCs that PIEZO1, a bona fide mechanosensitive ion channel, promotes the proliferative and regenerative function during skeletal muscle regeneration.

scholarly journals Roles of IL-1α/β in regeneration of cardiotoxin-injured muscle and satellite cell function

2018 ◽  
Vol 315 (1) ◽  
pp. R90-R103 ◽  
Author(s):  
Chayanit Chaweewannakorn ◽  
Masahiro Tsuchiya ◽  
Masashi Koide ◽  
Hiroyasu Hatakeyama ◽  
Yukinori Tanaka ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Satellite Cells ◽  
Muscle Regeneration ◽  
Cell Function ◽  
Inflammatory Responses ◽  
Cell Types ◽  
Skeletal Muscle Regeneration ◽  
Double Knockout ◽  
Positive Role

Skeletal muscle regeneration after injury is a complex process involving interactions between inflammatory microenvironments and satellite cells. Interleukin (IL)-1 is a key mediator of inflammatory responses and exerts pleiotropic impacts on various cell types. Thus, we aimed to investigate the role of IL-1 during skeletal muscle regeneration. We herein show that IL-1α/β-double knockout (IL-1KO) mice exhibit delayed muscle regeneration after cardiotoxin (CTX) injection, characterized by delayed infiltrations of immune cells accompanied by suppressed local production of proinflammatory factors including IL-6 and delayed increase of paired box 7 (PAX7)-positive satellite cells postinjury compared with those of wild-type (WT) mice. A series of in vitro experiments using satellite cells obtained from the IL-1KO mice unexpectedly revealed that IL-1KO myoblasts have impairments in terms of both proliferation and differentiation, both of which were reversed by exogenous IL-1β administration in culture. Intriguingly, the delay in myogenesis was not attributable to the myogenic transcriptional program since MyoD and myogenin were highly upregulated in IL-1KO cells, instead appearing, at least in part, to be due to dysregulation of cellular fusion events, possibly resulting from aberrant actin regulatory systems. We conclude that IL-1 plays a positive role in muscle regeneration by coordinating the initial interactions among inflammatory microenvironments and satellite cells. Our findings also provide compelling evidence that IL-1 is intimately engaged in regulating the fundamental function of myocytes.

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