Influence of sexual dimorphism on satellite cell regulation and inflammatory response during skeletal muscle regeneration.

After injury, skeletal muscle regenerates thanks to the key role of satellite cells (SC). The regeneration process is supported and coordinated by other cell types among which immune cells. Among the mechanisms involved in skeletal muscle regeneration, a sexual dimorphism, involving sex hormones and more particularly estrogens, has been suggested. However, the role of sexual dimorphism on skeletal muscle regeneration is not fully understood, likely to the use of various experimental settings in both animals and human. This review aims at addressing how sex and estrogens regulate both the SC and the inflammatory response during skeletal muscle regeneration by considering the different experimental designs used in both animal models (i.e., ovarian hormone deficiency, estrogen replacement or supplementation, treatments with estrogen receptors agonists/antagonists and models knockout for estrogen receptors) and human (hormone therapy replacement, pre vs. postmenopausal, menstrual cycle variation…).

Kinetics of skeletal muscle regeneration after mild and severe muscle damage induced by electrically-evoked lengthening contractions.

Post-injury skeletal muscle regeneration requires interactions between myogenic and non-myogenic cells. Our knowledge on the regeneration process is mainly based on models using toxic, chemical, or physical (e.g., based on either muscle freezing or crushing) injury. Strikingly, the time course and magnitude of changes in the number of cells involved in muscle regeneration have been poorly described in relation to mild and severe muscle damage induced by electrically-evoked lengthening contractions. We investigated for the first time the kinetics and magnitude of changes in mononuclear cells in relation to the extent of muscle damage. Mild and severe injury were induced in vivo in the mouse gastrocnemius muscle by 1 and 30 electrically-evoked lengthening contractions, respectively. Several days after muscle damage, functional analysis of maximal torque production and histological investigations were performed to assess the related cellular changes. Torque recovery was faster after mild injury than after severe muscle damage. More necrotic and regenerating myofibers were observed after severe muscle damage as compared with mild injury, illustrating an association between functional and histological alterations. The kinetics of changes in muscle stem cells (total, proliferating, and differentiating), endothelial cells, fibro-adipogenic progenitors (FAPs), and macrophages in the regenerating muscle was similar in mild and severe models. However, the magnitude of changes in the number of differentiating muscle stem cells, hematopoietic cells, among which macrophages, and FAPs was higher in severe muscle damage. Collectively, our results show that the amount of myogenic and non-myogenic cells varies according to the extent of skeletal muscle injury to ensure efficient skeletal muscle regeneration while the kinetics of changes is independent of muscle tissue alterations. The possibility to experimentally modulate the extent of muscle damage will be useful to further investigate the cellular and molecular events involved in muscle regeneration.