{"database":"iProX","file_versions":[],"scores":null,"additional":{"omics_type":["Proteomics"],"submitter":["Lingqing Yuan"],"species":["Mus Musculus"],"full_dataset_link":["http://www.iprox.org/page/project.html?id=IPX0019672000"],"submitter_email":["allenylq@csu.edu.cn"],"submitter_affiliation":["the Second Xiangya Hospital, Central South University"],"sample_protocol":[""],"repository":["iProX"],"data_protocol":[""],"additional_accession":[]},"is_claimable":false,"name":"SIRT3-Enriched Small Extracellular Vesicles Provide a Means for Skeletal Muscle-Bone crosstalk during Exercise","description":"Endurance exercise (Exe) has shown reliable protective effects against bone loss in the elderly and postmenopausal women. However, the mechanisms underlying Exe-mediated muscle-bone crosstalk remain to be fully elucidated. Here, we demonstrated that Exe enhanced the secretion of skeletal muscle-derived small extracellular vesicles (Mus-sEVs), which served as critical mediators of inter-tissue communication. Exe-induced Mus-sEVs (Exe-sEVs) attenuated bone loss in both ovariectomized (OVX) and aged mice by promoting the osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs). Mechanistically, proteomic profiling revealed that the cargo of Exe-sEVs was enriched in ferroptosis-related pathway. Pharmacological activation of ferroptosis abolished the bone-protective effects of Exe-sEVs. Further investigations demonstrated that enrichment of sirtuin 3 (SIRT3) in Exe-sEVs suppressed ferroptosis by enhancing mitophagy, thereby promoting osteogenesis of BMSCs and mitigating OVX-induced osteoporosis. Furthermore, targeted delivery of SIRT3-overexpressing sEVs (SIRT3-sEVs) to bone using a BMSC-specific aptamer significantly alleviated bone loss in OVX mice. Collectively, our study elucidates a novel mechanism of exercise-mediated muscle-bone crosstalk and highlights Exe-sEVs as a promising therapeutic strategy for osteoporosis.","dates":{"publication":"Tue Sep 22 00:00:00 GMT+01:00 2026"},"accession":"PXD084620","cross_references":{"TAXONOMY":["10090"]}}