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Mechanisms of Muscle Injury, Repair, and Regeneration
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TLDR
The process of muscle injury, repair and regeneration that occurs in muscular dystrophy is used as an example of chronic muscle injury to highlight similarities and differences between the injury and repair processes that occur in acutely and chronically injured muscle.Abstract:
Skeletal muscle continuously adapts to changes in its mechanical environment through modifications in gene expression and protein stability that affect its physiological function and mass. However, mechanical stresses commonly exceed the parameters that induce adaptations, producing instead acute injury. Furthermore, the relatively superficial location of many muscles in the body leaves them further vulnerable to acute injuries by exposure to extreme temperatures, contusions, lacerations or toxins. In this article, the molecular, cellular, and mechanical factors that underlie muscle injury and the capacity of muscle to repair and regenerate are presented. Evidence shows that muscle injuries that are caused by eccentric contractions result from direct mechanical damage to myofibrils. However, muscle pathology following other acute injuries is largely attributable to damage to the muscle cell membrane. Many feaures in the injury-repair-regeneration cascade relate to the unregulated influx of calcium through membrane lesions, including: (i) activation of proteases and hydrolases that contribute muscle damage, (ii) activation of enzymes that drive the production of mitogens and motogens for muscle and immune cells involved in injury and repair, and (iii) enabling protein-protein interactions that promote membrane repair. Evidence is also presented to show that the myogenic program that is activated by acute muscle injury and the inflammatory process that follows are highly coordinated, with myeloid cells playing a central role in modulating repair and regeneration. The early-invading, proinflammatory M1 macrophages remove debris caused by injury and express Th1 cytokines that play key roles in regulating the proliferation, migration, and differentiation of satellite cells. The subsequent invasion by anti-inflammatory, M2 macrophages promotes tissue repair and attenuates inflammation. Although this system provides an effective mechanism for muscle repair and regeneration following acute injury, it is dysregulated in chronic injuries. In this article, the process of muscle injury, repair and regeneration that occurs in muscular dystrophy is used as an example of chronic muscle injury, to highlight similarities and differences between the injury and repair processes that occur in acutely and chronically injured muscle.read more
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Therapeutic Approaches to Skeletal Muscle Repair and Healing
TL;DR: Effective repair of skeletal muscle after severe injury is unlikely to be achieved with a single intervention, and for full functional recovery of muscle there is a need to control inflammation, stimulate regeneration, and limit fibrosis.
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Defects in sarcolemma repair and skeletal muscle function after injury in a mouse model of Niemann-Pick type A/B disease
Vladimir Michailowsky,H. Li,Bidyottam Mittra,Shama R. Iyer,Davi A. G. Mázala,Matthias Corrotte,Yan Wang,Eva R. Chin,Richard M. Lovering,Norma W. Andrews +9 more
TL;DR: Skeletal muscle fibers from ASM−/− mice have an impairment in intracellular Ca2+ handling that results in reducedCa2+ mobilization and a more rapid decline in peak Ca2- transients during repeated contraction-relaxation cycles.
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Preconditioning contractions prevent the delayed onset of myofibrillar dysfunction after damaging eccentric contractions.
Ryotaro Yamada,Koichi Himori,Daisuke Tatebayashi,Yuki Ashida,Kazumi Ikezaki,Hirohumi Miyata,Keita Kanzaki,Masanobu Wada,Håkan Westerblad,Takashi Yamada +9 more
TL;DR: PCs counteracted the delayed onset force depression and this could be explained by prevention of immune cell invasion, which resulted in decreased myeloperoxidase‐mediated ROS production, hence avoiding cell membrane disruption, calpain activation and degenerative changes in myosin and actin molecules.
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Biomimetic Scaffolds for Skeletal Muscle Regeneration
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Beneficial Role of Exercise in the Modulation of mdx Muscle Plastic Remodeling and Oxidative Stress.
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