Skeletal muscle-derived exosomes prevent osteoporosis by promoting osteogenesis

Skeletal muscle and bone are the major organs for physical activity, in which there is a parallel correlation between muscle mass and bone density throughout a lifetime. Osteoporosis is a systemic bone metabolic disorder caused by reduced bone formation and increased bone resorption. Based on the metabolic symbiosis relationship between skeletal muscle and bone, we hypothesis that skeletal muscle secretory factors could play constructive roles in osteoporosis. Exosomes have been verified to transfer bioactive factors among cells. However, the role of skeletal muscle derived-exosomes (SM-Exos) in osteoporosis is still unclear. In this study, we isolated the exosomes derived from denervated skeletal muscles intervened by neuromuscular electrical stimulation (DN + ES-Exo), and then injected these DN + ES-Exo into sarco-osteoporotic rats through tail vein. In vitro studies, we cocultured SM-Exos from different states with differentiated MC3T3-E1 osteoblasts. In brief, our research results demonstrate that SM-Exos could partially promote osteogenesis both in vivo and in vitro. Further, our findings indicate that skeletal muscle contraction induced by neuromuscular electrical stimulation (NMES) can reverse the incidence of sarco-osteoporosis to a certain degree, and DN + ES-Exo contributes to the improvement in osteoporosis by facilitating osteoblast differentiation. Then, we revealed that NMES might regulate several miRNAs in skeletal muscle, the miRNAs that are encapsulated by SM-Exos might be involved in osteogenic differentiation in a network manner. All in all, this study confirmed the effect of NMES on sarco-osteoporosis and explored the role of SM-Exos in the improvement osteoporosis, which provide an effective theoretical support for the physical therapy of clinical sarco-osteoporosis.