scholarly journals Periostin Is Required for the Maintenance of Muscle Fibers during Muscle Regeneration

2021 ◽  
Vol 22 (7) ◽  
pp. 3627
Author(s):  
Naoki Ito ◽  
Yuko Miyagoe-Suzuki ◽  
Shin’ichi Takeda ◽  
Akira Kudo
Keyword(s):  
Blood Vessels ◽  
Progenitor Cells ◽  
Muscle Regeneration ◽  
Muscle Fibers ◽  
Protective Role ◽  
Skeletal Muscle Regeneration ◽  
Matricellular Protein ◽  
Myotendinous Junction ◽  
Muscle Weight

Skeletal muscle regeneration is a well-organized process that requires remodeling of the extracellular matrix (ECM). In this study, we revealed the protective role of periostin, a matricellular protein that binds to several ECM proteins during muscle regeneration. In intact muscle, periostin was localized at the neuromuscular junction, muscle spindle, and myotendinous junction, which are connection sites between muscle fibers and nerves or tendons. During muscle regeneration, periostin exhibited robustly increased expression and localization at the interstitial space. Periostin-null mice showed decreased muscle weight due to the loss of muscle fibers during repeated muscle regeneration. Cultured muscle progenitor cells from periostin-null mice showed no deficiencies in their proliferation, differentiation, and the expression of Pax7, MyoD, and myogenin, suggesting that the loss of muscle fibers in periostin-null mice was not due to the impaired function of muscle stem/progenitor cells. Periostin-null mice displayed a decreased number of CD31-positive blood vessels during muscle regeneration, suggesting that the decreased nutritional supply from blood vessels was the cause of muscle fiber loss in periostin-null mice. These results highlight the novel role of periostin in maintaining muscle mass during muscle regeneration.

Lack of Smad3 signaling leads to impaired skeletal muscle regeneration

2012 ◽  
Vol 303 (1) ◽  
pp. E90-E102 ◽  
Author(s):  
Xiaojia Ge ◽  
Anuradha Vajjala ◽  
Craig McFarlane ◽  
Walter Wahli ◽  
Mridula Sharma ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Mitochondrial Biogenesis ◽  
Muscle Regeneration ◽  
Intracellular Signaling ◽  
Muscle Injury ◽  
Transforming Growth Factor ◽  
Tibialis Anterior Muscle ◽  
Skeletal Muscle Regeneration ◽  
Muscle Weight

Smad3 is a key intracellular signaling mediator for both transforming growth factor-β and myostatin, two major regulators of skeletal muscle growth. Previous published work has revealed pronounced muscle atrophy together with impaired satellite cell functionality in Smad3-null muscles. In the present study, we have further validated a role for Smad3 signaling in skeletal muscle regeneration. Here, we show that Smad3-null mice had incomplete recovery of muscle weight and myofiber size after muscle injury. Histological/immunohistochemical analysis suggested impaired inflammatory response and reduced number of activated myoblasts during the early stages of muscle regeneration in the tibialis anterior muscle of Smad3-null mice. Nascent myofibers formed after muscle injury were also reduced in number. Moreover, Smad3-null regenerated muscle had decreased oxidative enzyme activity and impaired mitochondrial biogenesis, evident by the downregulation of the gene encoding mitochondrial transcription factor A, a master regulator of mitochondrial biogenesis. Consistent with known Smad3 function, reduced fibrotic tissue formation was also seen in regenerated Smad3-null muscle. In conclusion, Smad3 deficiency leads to impaired muscle regeneration, which underscores an essential role of Smad3 in postnatal myogenesis. Given the negative role of myostatin during muscle regeneration, the increased expression of myostatin observed in Smad3-null muscle may contribute to the regeneration defects.

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

scholarly journals PEDF-derived peptide promotes skeletal muscle regeneration through its mitogenic effect on muscle progenitor cells

2015 ◽  
Vol 309 (3) ◽  
pp. C159-C168 ◽  
Author(s):  
Tsung-Chuan Ho ◽  
Yi-Pin Chiang ◽  
Chih-Kuang Chuang ◽  
Show-Li Chen ◽  
Jui-Wen Hsieh ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Cell Proliferation ◽  
Cyclin D1 ◽  
Satellite Cell ◽  
Muscle Regeneration ◽  
Muscle Fibers ◽  
Skeletal Muscle Regeneration ◽  
Satellite Cell Proliferation

In response injury, intrinsic repair mechanisms are activated in skeletal muscle to replace the damaged muscle fibers with new muscle fibers. The regeneration process starts with the proliferation of satellite cells to give rise to myoblasts, which subsequently differentiate terminally into myofibers. Here, we investigated the promotion effect of pigment epithelial-derived factor (PEDF) on muscle regeneration. We report that PEDF and a synthetic PEDF-derived short peptide (PSP; residues Ser93-Leu112) induce satellite cell proliferation in vitro and promote muscle regeneration in vivo. Extensively, soleus muscle necrosis was induced in rats by bupivacaine, and an injectable alginate gel was used to release the PSP in the injured muscle. PSP delivery was found to stimulate satellite cell proliferation in damaged muscle and enhance the growth of regenerating myofibers, with complete regeneration of normal muscle mass by 2 wk. In cell culture, PEDF/PSP stimulated C2C12 myoblast proliferation, together with a rise in cyclin D1 expression. PEDF induced the phosphorylation of ERK1/2, Akt, and STAT3 in C2C12 myoblasts. Blocking the activity of ERK, Akt, or STAT3 with pharmacological inhibitors attenuated the effects of PEDF/PSP on the induction of C2C12 cell proliferation and cyclin D1 expression. Moreover, 5-bromo-2′-deoxyuridine pulse-labeling demonstrated that PEDF/PSP stimulated primary rat satellite cell proliferation in myofibers in vitro. In summary, we report for the first time that PSP is capable of promoting the regeneration of skeletal muscle. The signaling mechanism involves the ERK, AKT, and STAT3 pathways. These results show the potential utility of this PEDF peptide for muscle regeneration.

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 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 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 Role of proinflammatory cytokines and growth factors in skeletal muscle regeneration

2016 ◽  
Vol 72 (8) ◽  
pp. 472-478
Author(s):  
Marta Milewska ◽  
Katarzyna Grzelkowska-Kowalczyk
Keyword(s):  
Skeletal Muscle ◽  
Growth Factors ◽  
Proinflammatory Cytokines ◽  
Muscle Regeneration ◽  
Molecular Mechanisms ◽  
Critical Role ◽  
Muscle Fibers ◽  
Skeletal Muscle Regeneration ◽  
Functional Efficiency

Skeletal muscle healing after injury can be divided into three distinct but overlapping phases. The destruction phase is characterized by rupture followed by necrosis of muscle fibers, formation of hematoma and inflammatory reaction. During the repair phase a necrotic tissue is phagocyted by macrophages, muscle fibers are regenerating and connective tissue scars are formed. The remodeling phase concerns the period when regenerating muscle fibers mature, scar contraction and reorganization occurs and the muscle recovers its functional efficiency. Proinflammatory cytokines (IL-1β, IL-6, IL-8, TNF-α) and growth factors (FGF, IGF, TGF-β, HGF) play a critical role in all phases of muscle repair. Moreover, chemokines expressed at early stages of myogenesis can regulate the survival and proliferation of myoblasts. Chemokines expressed in vivo in muscle cells can directly influence myogenesis, but can also act in a paracrine manner by recruiting the immune cells (macrophages) to injured skeletal muscles, which is crucial for the regeneration process. Identification of molecules regulating myogenesis, like cytokines, chemokines and growth factors, contributes to the exploration of molecular mechanisms that can improve muscle regeneration after injury, diseases, surgery and increase the effectiveness of cell transplantation.

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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