<scp>EPC</scp>‐derived exosomes promote osteoclastogenesis through Lnc<scp>RNA</scp>‐<scp>MALAT</scp>1

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