Wnt7a Suppresses Adipogenesis of Skeletal Muscle Mesenchymal Stem Cells and Fatty Infiltration Through the Alternative Wnt-Rho-YAP/TAZ Signaling Axis

ABSTRACT Intramuscular fatty infiltration in muscle injuries and diseases, caused by aberrant adipogenesis of fibro-adipogenic progenitors, negatively impacts function. Intramuscular delivery of Wnt7a offers a promising strategy to stimulate muscle regeneration but its effects on adipogenic conversion of fibro-adipogenic progenitors remain unknown. Here we show that Wnt7a inhibits adipogenesis of FAPs through the alternative Wnt-Rho-YAP/TAZ signaling that subsequently upregulates the canonical Wnt pathway. Furthermore, intramuscular injection of Wnt7a in vivo effectively suppresses fatty infiltration in mice. Our results collectively suggest Wnt7a as a potential protein-based therapeutic for inhibiting adipogenesis of FAPs and intramuscular fatty infiltration in pathological muscle injuries or diseases.