scholarly journals Role of endocrine factors and stem cells in skeletal muscle regeneration

2021 ◽  
Vol 75 ◽  
pp. 371-384
Author(s):  
Barbara Morawin ◽  
Agnieszka Zembroń-Łacny
Keyword(s):  
Skeletal Muscle ◽  
Skeletal Muscles ◽  
Modern Medicine ◽  
Molecular Medicine ◽  
Skeletal Muscle Regeneration ◽  
Cellular Mechanisms ◽  
Factors Affecting ◽  
Post Traumatic ◽  
Endocrine Factors

The process of reconstructing damaged skeletal muscles involves degeneration, inflammatory and immune responses, regeneration and reorganization, which are regulated by a number of immune-endocrine factors affecting muscle cells and satellite cells (SCs). One of these molecules is testosterone (T), which binds to the androgen receptor (AR) to initiate the expression of the muscle isoform of insulin-like growth factor 1 (IGF-1Ec). The interaction between T and IGF-1Ec stimulates the growth and regeneration of skeletal muscles by inhibiting apoptosis, enhancement of SCs proliferation and myoblasts differentiation. As a result of sarcopenia, muscle dystrophy or wasting diseases, the SCs population is significantly reduced. Regular physical exercise attenuates a decrease in SCs count, and thus elevates the regenerative potential of muscles in both young and elderly people. One of the challenges of modern medicine is the application of SCs and extracellular matrix scaffolds in regenerative and molecular medicine, especially in the treatment of degenerative diseases and post-traumatic muscle reconstruction. The aim of the study is to present current information on the molecular and cellular mechanisms of skeletal muscle regenera,tion, the role of testosterone and growth factors in the activation of SCs and the possibility of their therapeutic use in stimulating the reconstruction of damaged muscle fibers.

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

2019 ◽  
Vol 30 (12) ◽  
pp. 1553-1598 ◽  
Author(s):  
Francesca De Santa ◽  
Laura Vitiello ◽  
Alessio Torcinaro ◽  
Elisabetta Ferraro
Keyword(s):  
Skeletal Muscle ◽  
Muscle Regeneration ◽  
Macrophage Polarization ◽  
Skeletal Muscle Regeneration ◽  
Metabolic Remodeling

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

1996 ◽  
Vol 21 (4) ◽  
pp. 236-250 ◽  
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

scholarly journals Tenogenic Contribution to Skeletal Muscle Regeneration: The Secretome of Scleraxis Overexpressing Mesenchymal Stem Cells Enhances Myogenic Differentiation In Vitro

2020 ◽  
Vol 21 (6) ◽  
pp. 1965
Author(s):  
Maximilian Strenzke ◽  
Paolo Alberton ◽  
Attila Aszodi ◽  
Denitsa Docheva ◽  
Elisabeth Haas ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Muscle Regeneration ◽  
Skeletal Muscles ◽  
Myogenic Differentiation ◽  
Muscular Contraction ◽  
Myoblast Fusion ◽  
Skeletal Muscle Regeneration ◽  
Potential Candidate ◽  
Musculoskeletal Tissue

Integrity of the musculoskeletal system is essential for the transfer of muscular contraction force to the associated bones. Tendons and skeletal muscles intertwine, but on a cellular level, the myotendinous junctions (MTJs) display a sharp transition zone with a highly specific molecular adaption. The function of MTJs could go beyond a mere structural role and might include homeostasis of this musculoskeletal tissue compound, thus also being involved in skeletal muscle regeneration. Repair processes recapitulate several developmental mechanisms, and as myotendinous interaction does occur already during development, MTJs could likewise contribute to muscle regeneration. Recent studies identified tendon-related, scleraxis-expressing cells that reside in close proximity to the MTJs and the muscle belly. As the muscle-specific function of these scleraxis positive cells is unknown, we compared the influence of two immortalized mesenchymal stem cell (MSC) lines—differing only by the overexpression of scleraxis—on myoblasts morphology, metabolism, migration, fusion, and alignment. Our results revealed a significant increase in myoblast fusion and metabolic activity when exposed to the secretome derived from scleraxis-overexpressing MSCs. However, we found no significant changes in myoblast migration and myofiber alignment. Further analysis of differentially expressed genes between native MSCs and scleraxis-overexpressing MSCs by RNA sequencing unraveled potential candidate genes, i.e., extracellular matrix (ECM) proteins, transmembrane receptors, or proteases that might enhance myoblast fusion. Our results suggest that musculotendinous interaction is essential for the development and healing of skeletal muscles.

Effect of diltiazem on skeletal muscle 3-O-methylglucose transport in bacteremic rats

1989 ◽  
Vol 256 (3) ◽  
pp. R716-R721
Author(s):  
M. V. Westfall ◽  
M. M. Sayeed
Keyword(s):  
Escherichia Coli ◽  
Skeletal Muscle ◽  
Low Temperature ◽  
Skeletal Muscles ◽  
Cytochalasin B ◽  
Sugar Transport ◽  
Male Rats ◽  
Saline Control ◽  
Permeability Changes

This study examined whether alterations in cellular Ca2+ regulation contribute to previously observed changes in skeletal muscle sugar transport during bacteremia. Fasted male rats received saline (control) or bacteria (4 X 10(10) Escherichia coli/kg) intraperitoneally. Twelve hours later, basal and insulin-mediated 3-O-methylglucose (3MG) transport was measured in isolated soleus muscles. Measurements of 3MG transport in the presence of cytochalasin b or at a low temperature (0.5 degree C) indicated that altered sugar transport in bacteremic rat muscles was not due to nonspecific membrane permeability changes. To determine the role of Ca2+ in the pathogenesis of altered sugar transport during bacteremia, rats were treated with the Ca2+ antagonist diltiazem (DZ, 0.6-2.4 mg/kg) at various times (0, 0 + 7.5, 10 h) after saline or bacterial injection. In bacteremic rats given 2.4 mg/kg DZ at 10 h, basal and insulin-mediated transport were similar to control values. This dose of DZ had little effect on control muscles. The addition of 20 microM DZ to the incubation media did not affect basal or insulin-mediated 3MG transport in bacteremic rat muscles. Addition of the Ca2+ agonist BAY K 8644 to the incubation media had no effect on sugar transport in bacteremic rat muscles but caused alterations in control rat muscles that were comparable to those observed in bacteremia. These results suggest that alterations in Ca2+ regulation could contribute to the previously observed changes in sugar transport in skeletal muscles from bacteremic rats.

scholarly journals The role of TGF-β1 during skeletal muscle regeneration

2017 ◽  
Vol 41 (7) ◽  
pp. 706-715 ◽  
Author(s):  
Kamila Delaney ◽  
Paulina Kasprzycka ◽  
Maria Anna Ciemerych ◽  
Malgorzata Zimowska
Keyword(s):  
Skeletal Muscle ◽  
Muscle Regeneration ◽  
Skeletal Muscle Regeneration ◽  
Tgf Β1

scholarly journals In Vivo Activation of STAT3 Signaling in Satellite Cells and Myofibers in Regenerating Rat Skeletal Muscles

2002 ◽  
Vol 50 (12) ◽  
pp. 1579-1589 ◽  
Author(s):  
Katsuya Kami ◽  
Emiko Senba
Keyword(s):  
Skeletal Muscle ◽  
Satellite Cells ◽  
Muscle Regeneration ◽  
Intracellular Signaling ◽  
Skeletal Muscles ◽  
Early Stage ◽  
Skeletal Muscle Regeneration ◽  
Stat3 Signaling

Although growth factors and cytokines play critical roles in skeletal muscle regeneration, intracellular signaling molecules that are activated by these factors in regenerating muscles have been not elucidated. Several lines of evidence suggest that leukemia inhibitory factor (LIF) is an important cytokine for the proliferation and survival of myoblasts in vitro and acceleration of skeletal muscle regeneration. To elucidate the role of LIF signaling in regenerative responses of skeletal muscles, we examined the spatial and temporal activation patterns of an LIF-associated signaling molecule, the signal transducer and activator transcription 3 (STAT3) proteins in regenerating rat skeletal muscles induced by crush injury. At the early stage of regeneration, activated STAT3 proteins were first detected in the nuclei of activated satellite cells and then continued to be activated in proliferating myoblasts expressing both PCNA and MyoD proteins. When muscle regeneration progressed, STAT3 signaling was no longer activated in differentiated myoblasts and myotubes. In addition, activation of STAT3 was also detected in myonuclei within intact sarcolemmas of surviving myofibers that did not show signs of necrosis. These findings suggest that activation of STAT3 signaling is an important molecular event that induces the successful regeneration of injured skeletal muscles.

Role of myokines in exercise and metabolism

2007 ◽  
Vol 103 (3) ◽  
pp. 1093-1098 ◽  
Author(s):  
Bente Klarlund Pedersen ◽  
Thorbjörn C. A. Åkerström ◽  
Anders R. Nielsen ◽  
Christian P. Fischer
Keyword(s):  
Skeletal Muscle ◽  
Skeletal Muscles ◽  
Contractile Activity ◽  
Endocrine Effects ◽  
Skeletal Muscle Function ◽  
The Past ◽  
Exercise Induced ◽  
Immune Changes ◽  
Muscle Contractile

During the past 20 yr, it has been well documented that exercise has a profound effect on the immune system. With the discovery that exercise provokes an increase in a number of cytokines, a possible link between skeletal muscle contractile activity and immune changes was established. For most of the last century, researchers sought a link between muscle contraction and humoral changes in the form of an “exercise factor,” which could mediate some of the exercise-induced metabolic changes in other organs such as the liver and the adipose tissue. We suggest that cytokines and other peptides that are produced, expressed, and released by muscle fibers and exert either paracrine or endocrine effects should be classified as “myokines.” Since the discovery of interleukin (IL)-6 release from contracting skeletal muscle, evidence has accumulated that supports an effect of IL-6 on metabolism. We suggested that muscle-derived IL-6 fulfils the criteria of an exercise factor and that such classes of cytokines should be named “myokines.” Interestingly, recent research demonstrates that skeletal muscles can produce and express cytokines belonging to distinctly different families. Thus skeletal muscle has the capacity to express several myokines. To date the list includes IL-6, IL-8, and IL-15, and contractile activity plays a role in regulating the expression of these cytokines in skeletal muscle. The present review focuses on muscle-derived cytokines, their regulation by exercise, and their possible roles in metabolism and skeletal muscle function and it discusses which cytokines should be classified as true myokines.

scholarly journals Protective Effects of Sonic Hedgehog Against Ischemia/Reperfusion Injury in Mouse Skeletal Muscle via AKT/mTOR/p70S6K Signaling

2017 ◽  
Vol 43 (5) ◽  
pp. 1813-1828 ◽  
Author(s):  
Qiu Zeng ◽  
Qining Fu ◽  
Xuehu Wang ◽  
Yu Zhao ◽  
Hong Liu ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Sonic Hedgehog ◽  
Ischemia Reperfusion ◽  
Critical Role ◽  
Systemic Administration ◽  
Skeletal Muscle Regeneration ◽  
Protective Effects ◽  
Shh Signaling ◽  
Apoptosis Pathway

Background/Aims: Skeletal muscle ischemia/reperfusion (I/R) injury is a common and severe disease. Sonic hedgehog (Shh) plays a critical role in post-natal skeletal muscle regeneration. In the present study, the role of Shh in skeletal muscle I/R injury and the mechanisms involved were investigated. Methods: The expression of Shh, AKT/mTOR/p70S6K and apoptosis pathway components were evaluated following tourniquet-induced skeletal muscle I/R injury. Then, mice were subjected to systemic administration of cyclopamine or one-shot treatment of a plasmid encoding the human Shh gene (phShh) to examine the effects of Shh on I/R injury. Moreover, mice were subjected to systemic administration of NVP-BEZ235 to investigate the role of the AKT/mTOR/p70S6K pathway in Shh-triggered skeletal muscle protection. Results: We found that the levels of Shh, AKT/mTOR/p70S6K pathway components and Cleaved Caspase 3 and the Bax/Bcl2 ratio initially increased and then decreased at different time points post-I/R injury. Moreover, Shh protected skeletal muscle against I/R injury by alleviating muscle destruction, reducing interstitial fibrosis and inhibiting apoptosis, and these protective effects were abrogated when the AKT/mTOR/p70S6K pathway was inhibited. Conclusion: Collectively, these data suggest that Shh signaling exerts a protective role through the AKT/mTOR/p70S6K signaling pathway during skeletal muscle I/R injury. Thus, Shh signaling may be a therapeutic target for protecting skeletal muscle from I/R injury.

scholarly journals Boosting The Peripheral Immune Response in the Skeletal Muscles Improved Motor Function in ALS Transgenic Mice

2021 ◽  
Author(s):  
Maria Chiara Trolese ◽  
Carlotta Scarpa ◽  
Valentina Melfi ◽  
Paola Fabbrizio ◽  
Francesca Sironi ◽  
...  
Keyword(s):  
Immune Response ◽  
Nervous System ◽  
Inflammatory Response ◽  
Muscle Regeneration ◽  
Skeletal Muscles ◽  
Skeletal Muscle Regeneration ◽  
Limiting Factors ◽  
Disease Stage ◽  
Peripheral Compartment

Abstract Background: Monocyte chemoattractant protein 1 (MCP1/CCL2) is one of the most powerful pro-inflammatory chemokines. However, its signalling is pivotal in driving axonal and muscle regeneration following injury. We previously showed that MCP1 is strongly upregulated in the nervous system of slow-progressing than fast-progressing SOD1G93A mice, which are characterised by a poor immune response that leads to a massive nerve and muscle degeneration.Methods: To assess the MCP1-mediated therapeutic role, we boosted the chemokine along the motor unit of the two SOD1G93A ALS models through a single intramuscular injection of a scAAV9 vector engineered with the Mcp1 gene (scAAV9_MCP1) at the pre-symptomatic disease stage.Results: Our observations revealed that slow-progressing SOD1G93A mice responded positively to the scAAV9_MCP1 injection anticipating the activation of the immune response, which sustained the pro-regenerative programme within nerves and skeletal muscles, eventually slackening the symptoms progression. Conversely, fast-progressing SOD1G93A mice exhibited an adverse response to the treatment, exacerbating the toxic inflammatory response in the periphery, resulting in worsened motor ability late in the disease.Intriguingly, our data suggested a novel pleiotropic role of MCP1 in the nervous system of SOD1G93A mice capable of promoting axon regeneration and modulating neuroinflammation, with the overall effect of preventing neurodegeneration.Conclusions: We provided direct evidence underlying the pivotal role of the immune response in promoting and governing skeletal muscle regeneration and thus the speed of ALS progression. The comparison study performed in fast- and slow-progressing SOD1G93A mice spotlights the nature and temporal activation of the inflammatory response as limiting factors to protect the peripheral compartment and interfere with the disease course tangibly. Altogether, these observations highlight the immune response as a key determinant for disease variability and proffer a reasonable explanation for the failure of systemic immunomodulatory treatments suggesting new potential strategies to hamper ALS progression.

scholarly journals Macrophages in Skeletal Muscle Dystrophies, An Entangled Partner

2021 ◽  
pp. 1-23
Author(s):  
Theret Marine ◽  
Saclier Marielle ◽  
Messina Graziella ◽  
Rossi M.V. Fabio
Keyword(s):  
Skeletal Muscle ◽  
Endothelial Cells ◽  
Muscle Regeneration ◽  
Genetic Diseases ◽  
Fatty Infiltration ◽  
Skeletal Muscle Regeneration ◽  
Muscular Dystrophies ◽  
Pathogenic Role ◽  
Muscle Remodeling

While skeletal muscle remodeling happens throughout life, diseases that result in its dysfunction are accountable for many deaths. Indeed, skeletal muscle is exceptionally capable to respond to stimuli modifying its homeostasis, such as in atrophy, hypertrophy, regeneration and repair. In particular conditions such as genetic diseases (muscular dystrophies), skeletal muscle’s capacity to remodel is strongly affected and undergoes continuous cycles of chronic damage. This induces scarring, fatty infiltration, as well as loss of contractibility and of the ability to generate force. In this context, inflammation, primarily mediated by macrophages, plays a central pathogenic role. Macrophages contribute as the primary regulators of inflammation during skeletal muscle regeneration, affecting tissue-resident cells such as myogenic cells and endothelial cells, but also fibro-adipogenic progenitors, which are the main source of the fibro fatty scar. During skeletal muscle regeneration their function is tightly orchestrated, while in dystrophies their fate is strongly disturbed, resulting in chronic inflammation. In this review, we will discuss the latest findings on the role of macrophages in skeletal muscle diseases, and how they are regulated.

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