The Role of Hypoxia and Hypoxia Signaling in Skeletal Muscle Physiology

Abstract

Hypoxia and hypoxia signaling play an integral role in regulating skeletal muscle physiology. Environmental hypoxia and tissue hypoxia in muscles cue for their appropriate physiological response and adaptation, and cause an array of cellular and metabolic changes. In addition, muscle stem cells (satellite cells), exist in a hypoxic state, and this intrinsic hypoxic state correlates with their quiescence and stemness. The mechanisms of hypoxia‐mediated regulation of satellite cells and myogenesis are yet to be characterized, and their seemingly contradicting effects reported leave their exact roles somewhat perplexing. This review summarizes the recent findings on the effect of hypoxia and hypoxia signaling on the key aspects of muscle physiology, namely, stem cell maintenance and myogenesis with a particular attention given to distinguish the intrinsic versus local hypoxia in an attempt to better understand their respective regulatory roles and how their relationship affects the overall response. This review further describes their mechanistic links and their possible implications on the relevant pathologies and therapeutics.

Transient hypoxia followed by progressive reoxygenation is required for efficient skeletal muscle repair through Rev-ERBα modulation

“…In the literature, the impact of hypoxia on the fate of MuSCs has been mainly evaluated by in vitro studies and has led to controversial results 42 , in particular concerning the effect of hypoxia on MuSC proliferation. Indeed, some studies show that hypoxia promotes myogenic proliferation 43,44 while some others demonstrate the opposite 24,45,46 .…”

Editorial: Application of innovative techniques in genetic and cellular therapies

“…Much of the recent innovation has therefore focused on the process of “priming.” In the context of priming, the induction of cellular quiescence has gained much attention due to its close relationship with the regenerative capacity of cells. Indeed, finding the appropriate method of inducing quiescence in progenitor cells has made a significant difference to the regenerative outcomes in skeletal muscle injuries ( Xie et al, 2018 ; Endo et al, 2023 ). Similarly, Chen et al described how quiescence preconditioning augmented the proliferation of the transplanted nucleus pulposus stem cells and improved the overall intervertebral disc regeneration.…”