Skeletal Muscle Loading Changes its Regenerative Capacity

Abstract

Whenever skeletal muscle insults occur, both by functional impositions or other injury forms, skeletal muscle repair (SMR) follows. The SMR succeeds when proper skeletal muscle regeneration and limited fibrosis ensue. Muscle fiber replenishment by fibrosis negatively affects the tissue quality and functionality and, furthermore, represents the worst post-injury phenotypic adaptation. Acute muscle injury treatment commonly follows the RICE method-rest, ice, compression, and elevation. This immediate immobilization seems to be beneficial to preserving the tissue structure and avoiding further destruction; however, if these interventions are delayed, the risk of muscle atrophy and its deleterious-related effects increase, with resultant impaired SMR. Moreover, a growing body of evidence shows positive skeletal muscle loading (SML) effects during SMR since it seems to effectively increase satellite cells (SCs) in their activation, proliferation, self-renewal, and differentiation capacities. Additionally, recent data show that SML may also influence the functions of other participants in SMR, compelling SMR to achieve less fibrotic accretion and accelerated muscle mass recovery. Moreover, given the SML effects on SCs, it is plausible to consider that these can increase the myofibers' basal myogenic potential. Thus, it seems relevant to scrutinize the possible acute and chronic SML therapeutic and prophylactic effects regarding the SMR process.

Key concepts in muscle regeneration: muscle “cellular ecology” integrates a gestalt of cellular cross-talk, motility, and activity to remodel structure and restore function

“…Excessive deposits of connective tissue are detrimental to muscle function in muscular dystrophy, as suggested over 40 years ago (Duance et al 1980 ); that impact is now well established in physiological experiments, computational modeling (Mann et al 2011 ; Martin et al 2016 ; Virgilio et al 2021 ), and the clinical literature (Best et al 2013 ; Lieber and Ward 2013 ; Teixeira and Duarte 2016 ). For example, the negative functional impact of extensive fibrosis and collagen deposition in skeletal and cardiac muscle of dystrophic mdx mice was demonstrated by functional gains after an anti-fibrosis treatment that reduced expression of collagens I and III.…”

“…For example, the negative functional impact of extensive fibrosis and collagen deposition in skeletal and cardiac muscle of dystrophic mdx mice was demonstrated by functional gains after an anti-fibrosis treatment that reduced expression of collagens I and III. Treatment attenuated dystrophic damage due to the tissue stiffness that affects myofibers (Huebner et al 2008 ), the satellite cell niche (Moyle et al 2020 ), satellite cell proliferation, and myogenesis (Teixeira and Duarte 2016 ).…”

The effect of Bu Zhong Yi Qi decoction on simulated weightlessness-induced muscle atrophy and its mechanisms

“…Satellite cells are skeletal muscular stem cells that are the primary source for muscle regeneration. Satellite cell dysfunction, representing impaired proliferation capacity or increased apoptosis, is suggested to contribute to the decreasing muscle regeneration in atrophy ( 5 , 6 ). Oxidative stress can be one of the triggers of muscle atrophy ( 7 ), while alterations of mitochondrial biogenesis and dynamics have been observed in prolonged unloading of muscle ( 8 , 9 ).…”

Biomechanical Behaviour and Biocompatibility of Ureidopyrimidinone-Polycarbonate Electrospun and Polypropylene Meshes in a Hernia Repair in Rabbits

“…One mechanism to explain this maladaptive remodelling response may be neotissue stiffness leading to disuse and stress shielding. It is well known that mechanical loading of skeletal muscle post-injury triggers many beneficial responses that enhance skeletal muscle regeneration and reduce fibrosis [41]. Under disuse, fibro-adipogenic precursors proliferate, differentiate into adipocytes and extracellular matrix-producing fibroblasts; thereby resulting in the accumulation of intramuscular fat and fibrotic tissue [42,43].…”