EPC ‐derived exosomes promote osteoclastogenesis through Lnc RNA ‐ MALAT 1

Bone repair involves bone resorption through osteoclastogenesis and the stimulation of neovascularization and osteogenesis by endothelial progenitor cells ( EPC s). However, the role of EPC s in osteoclastogenesis is unclear. In this study, we assess the effects of EPC ‐derived exosomes on the migration and osteoclastic differentiation of primary mouse bone marrow‐derived macrophages ( BMM s) in vitro using immunofluorescence, western blotting, RT ‐ PCR and Transwell assays. We also evaluated the effects of EPC ‐derived exosomes on the homing and osteoclastic differentiation of transplanted BMM s in a mouse bone fracture model in vivo. We found that EPC s cultured with BMM s secreted exosomes into the medium and, compared with EPC s, exosomes had a higher expression level of Lnc RNA ‐ MALAT 1. We confirmed that Lnc RNA ‐ MALAT 1 directly binds to miR‐124 to negatively control miR‐124 activity. Moreover, overexpression of miR‐124 could reverse the migration and osteoclastic differentiation of BMM s induced by EPC ‐derived exosomes. A dual‐luciferase reporter assay indicated that the integrin ITGB 1 is the target of miR‐124. Mice treated with EPC ‐derived exosome‐ BMM co‐transplantations exhibited increased neovascularization at the fracture site and enhanced fracture healing compared with those treated with BMM s alone. Overall, our results suggest that EPC ‐derived exosomes can promote bone repair by enhancing recruitment and differentiation of osteoclast precursors through Lnc RNA ‐ MALAT 1.