Muscle-Derived Extracellular Vesicles Improved Disuse-Induced Osteoporosis by Rebalancing Bone Formation and Bone Resorption

Osteoporosis is a highly prevalent skeletal bone disorder worldwide with characteristics of reduced bone mass and increased risk of osteoporotic fractures. It has been predicted to become a global challenge with the aging of the world population. However, the current therapy based on antiresorptive drugs and anabolic drugs have unwanted side effects. Although cell-based treatments have shown therapeutic effects for osteoporosis, there are still some limitations inhibiting the process of clinical application. In the present study, we developed EVs derived from skeletal muscle tissue (Mu-EVs) as a cell-free therapy to treat disuse-induced osteoporosis. Our results showed that Mu-EVs could be prepared easily and amountly from skeletal muscle tissues, and that these Mu-EVs had typical feature of extracellular vesicles. In vitro studies demonstrated that Mu-EVs from normal skeletal muscle could be phagocytized by bone marrow mesenchymal stem cells (BMSCs) and osteoclasts (OCs), and promoted osteogenic differentiation of BMSCs and inhibited OCs formation. Correspondingly, Mu-EVs from atrophic skeletal muscle attenuated the osteogenesis of BMSCs and strengthened the osteocalstogenesis of mononcytes. An in vivo experiment revealed that Mu-EVs could efficiently reverse the disuse-induced osteoporosis by enchancing bone formation and suppressing bone resorption. Collectively, our results suggest that Mu-EVs may be a potential cell-free therapy for osteoporosis treatment.Funding Information: This study was supported by the National Natural Science Foundation of China (Grant No.81600912), Key Project of Sichuan Province (Grant No.2019YFS0311 and 2019YFS0515), the Technology Innovation Research and Development Project of Chengdu (Grant No.2019-YF05-00705-SN), and the China Postdoctoral Science Foundation (Grant No.2019M653434).Conflict of Interests: The authors declare that they have no competing interests with this manuscript.Ethical Approval: All experiments were performed with the approval of the Ethics Committee of the State Key Laboratory of Oral Diseases, West China Hospital of Stomatology (Chengdu, Sichuan). All procedures were carried out according to the guidelines of the Animal Care Committee of Sichuan University.