Résumé :
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Satellite cells are now considered as true stem cells as they both participate to skeletal muscle repair by contributing to the formation of new myofibres and provide new quiescent satellite cells or reserve cells presenting the same properties. We have previously shown that in adult normal skeletal muscle, satellite cells are located close to capillaries. In vitro, endothelial cells and myogenic precursor cells (mpcs) have privileged interactions and may act in a paracrine way (Christov et al. 2007). One of the main molecular systems that regulate vascular homeostasis is the angiopoietin (Ang)/ Tie system. Particularly, Angiopoietin 1 (Ang1) binding to its tyrosine kinase Tie-2 receptor is required to maintain stabilization of the vessel and endothelial cell survival. Beside its role in the vascular system, Ang1/Tie-2 interaction has been also involved in hematopoietic stem cell quiescence by promoting their survival and maintain in the G0 phase. We have explored the role of Angs and Tie-2 system during in vitro myogenesis and in the regulation of myogenic cell population homeostasis. Expression of Ang1 decreased as cells differentiated, whereas Tie-2 expression increased. Both were upregulated in the reserve cells. Adding Ang1 to mpc cultures led to inhibition of both mpc growth and differentiation. Ang1 also protected mpcs from apoptosis through ERK1/2 signalling. These effects were mediated through Tie-2 receptor since a specific antagonist abolished Ang1 effect on mpcs. In whole mpc cultures, Ang1 treatment increased Pax7 expression and decreased MyoD expression. Inversely, silencing Tie-2 decreased Pax7 expression and increased MyoD expression, and increased the number of both proliferating and differentiating cells. In vivo, isolated quiescent satellite cells from both human and murine muscle expressed Tie-2 and Ang1. These results suggest that Ang1 binding to its receptor Tie-2 is involved in the regulation of the reserve cell pool within human myogenic precursor cell population.
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