Regenerating skeletal muscle contains transferrin and a transferrin-dependent growth factor (original) (raw)
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Reutilisation of tritiated thymidine in studies of regenerating skeletal muscle
Cell and Tissue Research, 1987
Two different aspects of tritiated thymidine (3H-Tdr) reutilisation in skeletal muscle were examined. Injection of a high dose (7 ~tCi/g) of 3H-Tdr into mice prior to crush injury of skeletal muscle resulted in heavy labelling (grain counts) of myotube nuclei 9 d later. In contrast, myotube nuclei were essentially unlabelled when a low dose (1 taCi/g) of 3H-Tdr was injected at similar times with respect to injury. It was concluded that labelling seen after the high dose was due to reutilisation of 3H-Tdr. (Such 3H-Tdr reutilisation can account for the results of Sloper et al. (1970) which previously supported the concept of a circulating muscle precursor cell.) When replicating muscle precursors were labelled directly with 3H-Tdr 48 h after injury, the percentages of labelled myotube nuclei and the distribution of nuclear grain counts were similar with either high or low dose.
Muscle regeneration: cellular and molecular events
In vivo (Athens, Greece)
Muscle injury induces strong changes in muscle cells and extracellular matrix. Muscle regeneration after injury has similarities to muscle development during embryogenesis and seems to follow the same procedure. The initial phase of muscle repair is characterized by inflammation and degeneration of the damaged tissue. Almost simultaneously, previous quiescent myogenic cells, called satellite cells, are activated, proliferate, differentiate and fuse to form multinucleated myofibers. Other non-muscle stem cells may also take part in this process. Secreted factors, such as hepatocyte growth factor (HGF), fibroblast growth factors (FGFs), transforming growth factor-betas (TGF-betas), insulin-like growth factors (IGFs), tumour necrosis factor alpha (TNFalpha) and others, are released during muscle repair and guide muscle regeneration, however, their exact functions and effects on muscle remodeling remain unknown. Intensive research is currently addressing the regenerative mechanisms whic...
Journal of musculoskeletal & neuronal interactions, 2014
Heat stress could promote skeletal muscle regeneration. But, in the regeneration process, effects of heat stress on myogenic cells and the regulating factors is unknown. Therefore, Influences of heat stress soon after injury on distribution of the myogenic cells and chronological changes in expression of MyoD and myogenin were examined. The first peak of MyoD expression was temporally correlated with the time when proliferating satellite cells began to appear, and the rapid decline of the MyoD expression from the first peak, with the appearance time of myoblasts, respectively in both the non-Heat and Heat groups. The first peak of myogenin expression was temporally correlated with the time when multinuclear cells began to form in the both groups. Due to the heat stress, proliferation and differentiation of myogenic cells and chronological changes in these factors were accelerated one day earlier than in the non-Heat group. As MyoD and myogenin are regulating factor of proliferation ...
Regeneration of Mammalian Skeletal Muscle: Basic Mechanisms and Clinical Implications
Current Pharmaceutical Design, 2010
Mammalian skeletal muscles can regenerate following injury and this response is mediated by a specific type of stem cell, the satellite cell. We review here the three main phases of muscle regeneration, including i) the initial inflammatory response and the dual role of macrophages as both scavengers involved in the phagocytosis of necrotic debris and promoters of myogenic differentiation, ii) the activation and differentiation of satellite cells and iii) the growth and remodeling of the regenerated muscle tissue. Nerve activity is required to support the growth of regenerated myofibers and the specification of muscle fiber types, in particular the activation of the slow gene program. We discuss the regeneration process in two different settings. Chronic degenerative diseases, such as muscular dystrophies, are characterized by repeated cycles of segmental necrosis and regeneration involving scattered myofibers. In these conditions the regenerative capacity of satellite cells becomes exhausted with time and fibrosis prevails. Acute traumatic injuries, such as strain injuries common in sport medicine, cause the rupture of large myofiber bundles leading to muscle regeneration and formation of scar tissue and new myotendinous junctions at the level of the rupture. Mechanical loading is essential for muscle regeneration, therefore, following initial immobilization to avoid the risk of reruptures, early remobilization is required to induce correct growth and orientation of regenerated myofibers. Finally, we discuss the causes of age-dependent decline in muscle regeneration potential and the possibility of boosting regeneration in aging muscle and in muscular dystrophies.
Basic Appl Myol, 2004
Macrophages drive muscle regeneration and repair by removing necrotic material and producing key signaling molecules. The array of cytokines/growth factors produced by macrophages and myogenic cells stimulates the proliferation, migration and differentiation of satellite cells. Although the details of such processes are only partially understood, it is known that the administration of purified growth factors can improve the final outcome after traumatic muscle injuries. Also, such approach has proved to be beneficial in myoblast transplantation experiments in animal models. The translation of such procedures into therapeutic protocols is, however, hampered by high costs and the somewhat oversimplified biochemical input compared to the physiological signal network. We have previously reported that peritoneal macrophages could secrete factors capable of increasing the myoblast/myotube yield in cultures of primary rat myoblasts. Recently, we observed that a macrophage cell line could be stimulated to produce a conditioned medium that specifically enhances the proliferation of cultured neonatal primary myoblasts from mouse, rat, chicken, and human fetal myoblasts. The factors did not inhibit differentiation and led to a striking increase in the rate of contractile myotube formation. The factors could also enhance muscle regenerative processes in vivo, thereby suggesting a potential role as an economical and effective tool for the treatment of traumatic and disease-related muscle injuries. Further experiments in this direction and the biochemical characterization of the macrophage-produced myogenic factors are presently underway. The possibility to use the macrophage factors to improve the myoblast yield from diseased-muscle biopsies is also under investigation. Abbreviations: MCM: macrophage-conditioned medium.
Experimental Cell Research, 1989
Autoradiographic studies were carried out on regenerating muscles of adult chickens. Three different muscles of hens were injured, and tritiated thymidine (1 @X/g) was injected at various times after injury to label replicating muscle precursors. Detailed comparisons of grain counts over premitotic nuclei in samples removed one hour after injection of tritiated thymidine, and of postmitotic myotube nuclei in samples removed 10 days after injury (when labeled precursors had fused to form myotubes), revealed how many times some labeled precursors had divided before fusing into myotubes. DNA synthesis in muscle precursors was initiated 30 h after injury. Grain counts of myotube nuclei indicated that many muscle precursors labeled at the onset of myogenic cell proliferation had divided only once, or twice, before fusing into myotubes. The relationship of these in vivo results to the cell lineage model of myogenesis is discussed.
Growth factors improve muscle healing in vivo
The Journal of Bone and Joint Surgery, 2000
I njury to muscles is very common. We have previously observed that basic fibroblast growth factor (b-FGF), insulin growth factor type 1 (IGF-1) and nerve growth factor (NGF) are potent stimulators of the proliferation and fusion of myoblasts in vitro. We therefore injected these growth factors into mice with lacerations of the gastrocnemius muscle. The muscle regeneration was evaluated at one week by histological staining and quantitative histology. Muscle healing was assessed histologically and the contractile properties were measured one month after injury.
Physiological Reports, 2016
Skeletal muscle satellite cells are a muscle stem cell population that mediate posthatch muscle growth and repair. Satellite cells respond differentially to environmental stimuli based upon their fiber-type of origin. The objective of this study was to determine how temperatures below and above the in vitro control of 38°C affected the proliferation and differentiation of satellite cells isolated from the chicken anaerobic pectoralis major (p. major) or mixed fiber biceps femoris (b.femoris) muscles. The satellite cells isolated from the p. major muscle were more sensitive to both cold and hot temperatures compared to the b.femoris satellite cells during both proliferation and differentiation. The expressions of myogenic regulatory transcription factors were also different between satellite cells from different fiber types. MyoD expression, which partially regulates proliferation, was generally expressed at higher levels in p. major satellite cells compared to the b.femoris satellite cells from 33 to 43°C during proliferation and differentiation. Similarly, myogenin expression, which is required for differentiation, was also expressed at higher levels in p. major satellite cells in response to both cold and hot temperatures during proliferation and differentiation than b. femoris satellite cells. These data demonstrate that satellite cells from the anaerobic p. major muscle are more sensitive than satellite cells from the aerobic b. femoris muscle to both hot and cold thermal stress during myogenic proliferation and differentiation.
Scientific Reports, 2016
The application of cryotherapy is widely used in sports medicine today. Cooling could minimize secondary hypoxic injury through the reduction of cellular metabolism and injury area. Conflicting results have also suggested cryotherapy could delay and impair the regeneration process. There are no definitive findings about the effects of cryotherapy on the process of muscle regeneration. The aim of the present study was to evaluate the effects of a clinical-like cryotherapy on inflammation, regeneration and extracellular matrix (ECM) remodeling on the Tibialis anterior (TA) muscle of rats 3, 7 and 14 days post-injury. It was observed that the intermittent application of cryotherapy (three 30-minute sessions, every 2 h) in the first 48 h post-injury decreased inflammatory processes (mRNA levels of TNF-α, NF-κB, TGF-β and MMP-9 and macrophage percentage). Cryotherapy did not alter regeneration markers such as injury area, desmin and Myod expression. Despite regulating Collagen I and III and their growth factors, cryotherapy did not alter collagen deposition. In summary, clinical-like cryotherapy reduces the inflammatory process through the decrease of macrophage infiltration and the accumulation of the inflammatory key markers without influencing muscle injury area and ECM remodeling. Skeletal muscle lesions are responsible for the majority of the functional limitations observed in sports and occupational medicine 1. After primary injury, muscle regeneration occurs in a highly orchestrated process that involves the activation of muscle satellite cells to proliferate and differentiate into a new muscle fiber 2 with a constant pattern irrespective of the cause (contusion, strain, or laceration). After muscle injury it is possible to observe four independent phases, despite their etiology: degeneration, inflammation, regeneration, and fibrosis 2-4. The activation and differentiation of satellite cells is characterized by the rapid upregulation of myogenic differentiation 1 (MyoD) and insulin-like growth factor 1 (IGF-1) 5,6. In addition, in vitro and in vivo studies indicate that anti-inflammatories such as interleukin-10 (IL-10) and transforming growth factor beta (TGF-β) and pro-inflammatory cytokines such as tumor necrosis factor alpha (TNF-α) and nuclear factor-κ B (NF-κ B) produced by macrophages could activate satellite cells, stimulating myoblast proliferation and differentiation into myotube formation 7,8. The fibrosis and remodeling phases of muscle regeneration involve the deposition of Collagen I and III fibers and reorganization of the tissue, which could be induced by TGF-β 9 , IGF-I 10 , and connective tissue growth factor (CTGF) 11. In addition, matrix metalloproteinases (MMPs) cooperatively degrade all components of the extracellular matrix (ECM) 12. MMP-2 (or gelatinase A) activity is concurrent with the regeneration of new myofibers probably due to degradation of type IV collagen of the basement membrane during myoblast proliferation, migration, and fusion. MMP-9 (or gelatinase B) activation is related to the early inflammatory phase and to the activation of satellite cells 13,14 .
Journal of Thermal Biology, 2021
Proteins secreted from skeletal muscle serving a signalling role have been termed myokines. Many of the myokines are exercise factors, produced and released in response to muscle activity. Cold exposures affecting muscle may occur in recreational, occupational and therapeutic settings. Whether muscle temperature independently affects myokine profile, is still to be elucidated. We hypothesized that manipulating muscle temperature by means of external cooling would change myokine production and release. In the present study we have established new models for cold exposure of muscle in vivo and in vitro where rat hind limb or cultured human myotubes were cooled to 18 • C. After a recovery period, muscle tissue, cells and culture media were harvested for further analysis by qPCR and immunoassays. Expression of several myokine genes were significantly increased after cold exposure in both models: in rat muscle, mRNA levels of CCL2 (p = 0.04), VEGFA (p = 0.02), CXCL1 (p = 0.02) and RBM3 (p = 0.02) increased while mRNA levels of IL-6 (p = 0.03) were decreased; in human myotubes, mRNA levels of IL6 (p = 0.01), CXCL8 (p = 0.04), VEGFA (p = 0.03) and CXCL1 (p < 0.01) were significantly increased, as well as intracellular protein levels of IL-8 (CXCL8 gene product; p < 0.01). The corresponding effect on myokine secretion was not observed, on the contrary, IL-8 (p = 0.02) and VEGF (VEGFA gene product) p < 0.01) concentrations in culture media were reduced after cold exposure in vitro. In conclusion, cold exposure of muscle in vivo and in vitro had an effect on the production and release of several known exercise-related myokines. Myokine expression at the level of mRNA and protein was increased by cold exposure, whereas secretion tended to be decreased.