scholarly journals Increased fat deposition in injured skeletal muscle is regulated by sex-specific hormones

2012 ◽  
Vol 302 (3) ◽  
pp. R331-R339 ◽  
Author(s):  
Matthew J. McHale ◽  
Zaheer U. Sarwar ◽  
Damon P. Cardenas ◽  
Laurel Porter ◽  
Anna S. Salinas ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Muscle Regeneration ◽  
Inflammatory Cells ◽  
Fat Deposition ◽  
Skeletal Muscle Regeneration ◽  
High Dose ◽  
Ovariectomized Mice ◽  
Intermuscular Fat ◽  
Males And Females ◽  
Injury Models

Sex differences in skeletal muscle regeneration are controversial; comparisons of regenerative events between sexes have not been rigorously defined in severe injury models. We comprehensively quantified inflammation and muscle regeneration between sexes and manipulated sex-specific hormones to determine effects on regeneration. Cardiotoxin injury was induced in intact, castrated and ovariectomized female and male mice; ovariectomized mice were replaced with low- or high-dose 17-β estradiol (E2) or progesterone (P4). Extent of injury was comparable between intact mice, but females were more efficient in removal of necrotic debris, despite similar tissue levels of inflammatory cells and chemokines. Myofiber size during regeneration was equivalent between intact mice and after castration or ovariectomy (OVX) but was decreased ( P < 0.001) in ovariectomized mice with high-dose E2 replacement. Intermuscular adipocytes were absent in uninjured muscle, whereas adipocyte area was increased among regenerated myofibers in all groups. Interestingly, intermuscular fat was greater ( P = 0.03) in intact females at day 14 compared with intact males. Furthermore, castration increased ( P = 0.01) and OVX decreased adipocyte accumulation. After OVX, E2, but not P4, replacement decreased ( P ≤ 0.03) fat accumulation. In conclusion, sex-dependent differences in regeneration consisted of more efficient removal of necrosis and increased fat deposition in females with similar injury, inflammation, and regenerated myofiber size; high-dose E2 decreased myofiber size and fat deposition. Adipocyte accumulation in regenerating muscle was influenced by sex-specific hormones. Recovery following muscle injury was different between males and females, and sex-specific hormones contributed to these differences, suggesting that sex-specific treatments could be beneficial after injury.

scholarly journals Bi-phasic effect of gelatin in myogenesis and skeletal muscle regeneration

2021 ◽  
Author(s):  
Xiaoling Liu ◽  
Er Zu ◽  
Xinyu Chang ◽  
Xiaowei Ma ◽  
Ziqi Wang ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Antioxidant System ◽  
Muscle Regeneration ◽  
Chain Complex ◽  
Skeletal Muscle Regeneration ◽  
High Dose ◽  
Mild Stress ◽  
Ecm Remodeling ◽  
Ros Accumulation ◽  
Intracellular Ros

Skeletal muscle regeneration requires extracellular matrix (ECM) remodeling, including an acute and transient breakdown of collagen that produces gelatin. Although the physiological function of this process is unclear, it has inspired us to apply gelatin to injured skeletal muscle for a potential pro-regenerative effect. Here we elaborate on a bi-phasic effect of gelatin in skeletal muscle regeneration, mediated by hormetic effects of reactive oxygen species (ROS). Low-dose gelatin stimulates ROS production from NADPH oxidase 2 (NOX2) and simultaneously upregulates antioxidant system for cellular defense, reminiscent of the adaptive compensatory process during mild stress. This response triggers the release of myokine IL-6 that stimulates myogenesis and facilitates muscle regeneration. By contrast, high-dose gelatin stimulates ROS overproduction from NOX2 and mitochondrial chain complex, and ROS accumulation by suppressing antioxidant system, triggering release of TNFα, which inhibits myogenesis and regeneration. Our results have revealed a bi-phasic role of gelatin in regulating skeletal muscle repair mediated by intracellular ROS, antioxidant system, and cytokines (IL-6 and TNFα) signaling.

scholarly journals The COX-2 pathway is essential during early stages of skeletal muscle regeneration

2004 ◽  
Vol 287 (2) ◽  
pp. C475-C483 ◽  
Author(s):  
Brenda A. Bondesen ◽  
Stephen T. Mills ◽  
Kristy M. Kegley ◽  
Grace K. Pavlath
Keyword(s):  
Skeletal Muscle ◽  
Muscle Regeneration ◽  
Inflammatory Cells ◽  
Skeletal Muscle Regeneration ◽  
Cellular Processes ◽  
Early Stages ◽  
Inflammatory Drugs ◽  
Cox 2 ◽  
Anti Inflammatory

Skeletal muscle regeneration comprises several overlapping cellular processes, including inflammation and myogenesis. Prostaglandins (PGs) may regulate muscle regeneration, because they modulate inflammation and are involved in various stages of myogenesis in vitro. PG synthesis is catalyzed by different isoforms of cyclooxygenase (COX), which are inhibited by nonsteroidal anti-inflammatory drugs. Although experiments employing nonsteroidal anti-inflammatory drugs have implicated PGs in tissue repair, how PGs regulate muscle regeneration remains unclear, and the potentially distinct roles of different COX isoforms have not been investigated. To address these questions, a localized freeze injury was induced in the tibialis anterior muscles of mice chronically treated with either a COX-1- or COX-2-selective inhibitor (SC-560 and SC-236, respectively), starting before injury. The size of regenerating myofibers was analyzed at time points up to 5 wk after injury and found to be decreased by SC-236 and in COX-2−/− muscles, but unaffected by SC-560. In contrast, SC-236 had no effect on myofiber growth when administered starting 7 days after injury. The attenuation of myofiber growth by SC-236 treatment and in COX-2−/− muscles is associated with decreases in the number of myoblasts and intramuscular inflammatory cells at early times after injury. Together, these data suggest that COX-2-dependent PG synthesis is required during early stages of muscle regeneration and thus raise caution about the use of COX-2-selective inhibitors in patients with muscle injury or disease.

scholarly journals Macrophages Are Key Regulators of Stem Cells during Skeletal Muscle Regeneration and Diseases

2019 ◽  
Vol 2019 ◽  
pp. 1-20 ◽  
Author(s):  
Junio Dort ◽  
Paul Fabre ◽  
Thomas Molina ◽  
Nicolas A. Dumont
Keyword(s):  
Skeletal Muscle ◽  
Muscle Regeneration ◽  
Inflammatory Cells ◽  
Cell Types ◽  
Skeletal Muscle Regeneration ◽  
Cellular Interactions ◽  
Muscle Disorders ◽  
New Therapeutic Approaches ◽  
Inflammatory Phenotype ◽  
Muscle Homeostasis

Muscle regeneration is a closely regulated process that involves a variety of cell types such as satellite cells, myofibers, fibroadipogenic progenitors, endothelial cells, and inflammatory cells. Among these different cell types, macrophages emerged as a central actor coordinating the different cellular interactions and biological processes. Particularly, the transition of macrophages from their proinflammatory to their anti-inflammatory phenotype was shown to regulate inflammation, myogenesis, fibrosis, vascularization, and return to homeostasis. On the other hand, deregulation of macrophage accumulation or polarization in chronic degenerative muscle disorders was shown to impair muscle regeneration. Considering the key roles of macrophages in skeletal muscle, they represent an attractive target for new therapeutic approaches aiming at mitigating various muscle disorders. This review aims at summarizing the novel insights into macrophage heterogeneity, plasticity, and functions in skeletal muscle homeostasis, regeneration, and disease.

scholarly journals Simvastatin Impairs the Inflammatory and Repair Phases of the Postinjury Skeletal Muscle Regeneration

2018 ◽  
Vol 2018 ◽  
pp. 1-13 ◽  
Author(s):  
Iwona Otrocka-Domagała ◽  
Katarzyna Paździor-Czapula ◽  
Tomasz Maślanka
Keyword(s):  
Skeletal Muscle ◽  
Muscle Regeneration ◽  
Muscle Injury ◽  
Inflammatory Cells ◽  
Skeletal Muscle Regeneration ◽  
Regenerative Capacity ◽  
Inflammatory Phase ◽  
M1 Macrophage ◽  
Increased Risk ◽  
Repair Phase

Background. Recent clinical data have suggested that the chronic use of high-lipophilic statins impairs the regenerative capacity of skeletal muscle. Because this activity of statins is poorly understood, we aimed to investigate the effect of simvastatin (SIM) on postinjury myofibre regeneration. Methods. The porcine model was used in this study. The animals were divided into two groups: nontreated (control; n=24) and SIM-treated (40 mg/day; n=24). On the 15th day (day 0) of the experiment, a bupivacaine hydrochloride- (BPVC-) induced muscle injury was established, and the animals were sacrificed in the following days after muscle injury. The degree of regeneration was assessed based on histopathological and immunohistochemical examinations. The presence and degree of extravasation, necrosis, and inflammation in the inflammatory phase were assessed, whereas the repair phase was evaluated based on the numbers of muscle precursor cells (MPCs), myotube and young myofibres. Results. In the inflammatory phase, SIM increased the distribution and prolonged the period of extravasation, prolonged the duration of necrosis, and prolonged and enhanced the infiltration of inflammatory cells. In the repair phase, SIM delayed and prolonged the activity of MPCs, delayed myotube formation, and delayed and decreased the formation of young myofibres. Our results indicated that SIM did not improve blood vessel stabilization at the site of the injury, did not exert an anti-inflammatory effect, prolonged and enhanced the inflammatory response, and impaired MPC activity, differentiation, and fusion. Moreover, SIM appeared to reduce M1 macrophage activity, resulting in slower removal of necrotic debris and sustained necrosis. Conclusion. This study shows that SIM negatively affects the inflammatory and repair phases of the postinjury muscle regeneration. These findings are unique, strengthen the available knowledge on the side effects of SIM, and provide evidence showing that statin therapy is associated with an increased risk of impairment of the regenerative capacity of muscle.

scholarly journals The Role of Satellite Cells in Skeletal Muscle Regeneration—The Effect of Exercise and Age

Biology ◽  
2021 ◽  
Vol 10 (10) ◽  
pp. 1056
Author(s):  
Agnieszka Kaczmarek ◽  
Mateusz Kaczmarek ◽  
Maria Ciałowicz ◽  
Filipe Manuel Clemente ◽  
Paweł Wolański ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Satellite Cells ◽  
Muscle Regeneration ◽  
Inflammatory Cells ◽  
Skeletal Muscle Regeneration ◽  
Vigorous Exercise ◽  
Fiber Damage ◽  
Current State ◽  
Ability To Regenerate ◽  
And Control

The population of satellite cells (mSCs) is highly diversified. The cells comprising it differ in their ability to regenerate their own population and differentiate, as well as in the properties they exhibit. The heterogeneity of this group of cells is evidenced by multiple differentiating markers that enable their recognition, classification, labeling, and characterization. One of the main tasks of satellite cells is skeletal muscle regeneration. Myofibers are often damaged during vigorous exercise in people who participate in sports activities. The number of satellite cells and the speed of the regeneration processes that depend on them affect the time structure of an athlete’s training. This process depends on inflammatory cells. The multitude of reactions and pathways that occur during the regeneration process results in the participation and control of many factors that are activated and secreted during muscle fiber damage and at different stages of its regeneration. However, not all of them are well understood yet. This paper presents the current state of knowledge on satellite cell-dependent skeletal muscle regeneration. Studies describing the effects of various forms of exercise and age on this process were reviewed.

scholarly journals Recent Trends in Injury Models to Study Skeletal Muscle Regeneration and Repair

2020 ◽  
Vol 7 (3) ◽  
pp. 76 ◽  
Author(s):  
Sydnee T. Sicherer ◽  
Rashmi S. Venkatarama ◽  
Jonathan M. Grasman
Keyword(s):  
Skeletal Muscle ◽  
Muscle Tissue ◽  
Muscle Regeneration ◽  
Muscle Injury ◽  
Large Scale ◽  
Skeletal Muscle Regeneration ◽  
Muscle Injuries ◽  
Injury And Repair ◽  
Injury Models

Skeletal muscle injuries that occur from traumatic incidents, such as those caused by car accidents or surgical resections, or from injuries sustained on the battlefield, result in the loss of functionality of the injured muscle. To understand skeletal muscle regeneration and to better treat these large scale injuries, termed volumetric muscle loss (VML), in vivo injury models exploring the innate mechanisms of muscle injury and repair are essential for the creation of clinically applicable treatments. While the end result of a muscle injury is often the destruction of muscle tissue, the manner in which these injuries are induced as well as the response from the innate repair mechanisms found in muscle in each animal models can vary. This targeted review describes injury models that assess both skeletal muscle regeneration (i.e., the response of muscle to myotoxin or ischemic injury) and skeletal muscle repair (i.e., VML injury). We aimed to summarize the injury models used in the field of skeletal muscle tissue engineering, paying particular attention to strategies to induce muscle damage and how to standardize injury conditions for future experiments.

scholarly journals Bi-phasic effect of gelatin in myogenesis and skeletal muscle regeneration

2021 ◽  
Author(s):  
Xiao ling Liu ◽  
Er Zu ◽  
Xin Yu Chang ◽  
Zi Qi Wang ◽  
Xiang Ru Li ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Antioxidant System ◽  
Muscle Regeneration ◽  
Chain Complex ◽  
Skeletal Muscle Regeneration ◽  
High Dose ◽  
Mild Stress ◽  
Ecm Remodeling ◽  
Cellular Defense ◽  
Ros Accumulation

Skeletal muscle regeneration requires extracellular matrix (ECM) remodeling including an acute and transient breakdown of collagen that produces gelatin. However, the physiological function of such a remodeling process on muscle tissue repair is unclear. Here we elaborate on a bi-phasic effect of gelatin in skeletal muscle regeneration, mediated by hormetic effects of reactive oxygen species (ROS). Low-dose gelatin stimulates ROS production from NADPH oxidase 2 (NOX2) and simultaneously upregulates antioxidant system for cellular defense, reminiscent of the adaptive compensatory process during mild stress. This response triggers the release of myokine IL-6 which stimulates myogenesis and facilitates muscle regeneration. By contrast, high-dose gelatin stimulates ROS overproduction from NOX2 and mitochondrial chain complex, and ROS accumulation by suppressing antioxidant system, triggering release of TNFα, which inhibits myogenesis and regeneration. Our findings reveal gelatin-ROS-IL-6/TNFα signaling cascades underlying a hormetic response of myogenic cells to gelatin.

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