Mitochondrial components transferred by MSC-derived exosomes promoted bone regeneration under high salt microenvironment via DRP1/Wnt signaling  

作　　者：Yiming Wang Shuai Lin Liujing Chen Mingzhao Li Zilu Zhu Zimeng Zhuang Meilian Cai Han Zhang Chenyang Xing Weiran Li Ruili Yang 

机构地区：[1]Department of Orthodontics,School and Hospital of Stomatology,Peking University,Beijing 100081,China [2]National Clinical Research Center for Oral Diseases&National Engineering Laboratory for Digital and Material Technology of Stomatology,School and Hospital of Stomatology,Peking University,Beijing 100081,China [3]Beijing Key Laboratory of Digital Stomatology,School and Hospital of Stomatology,Peking University,Beijing 100081,China

出　　处：《Nano Research》2024年第9期8301-8315,共15页纳米研究（英文版）

基　　金：supported by the National Science and Technology Major Project of the Ministry of Science and Technology of China(No.2022YFA1105800);the National Natural Science Foundation of China(No.81970940(R.L.Y.));Research Foundation of Peking University School and Hospital of Stomatology(No.PKUSS20230103);Postdoctoral Fellowship Program of China Postdoctoral Science Foundation(No.GZC20230136).

摘　　要：Bone homeostasis relies on the dynamic balance of osteoblast mediated bone construction and osteoclast-based bone resorption processes,which has been reported to be controlled by various mineral ions.However,there is no direct evidence of the effect and the underlying mechanism of high salt stimulation on bone metabolism.In this study,we demonstrated that high salt stimulation promoted excessive mitochondrial fission mediated by dynamin-related protein 1 in mesenchymal stem cells,which resulted in impaired mitochondrial morphology and function.Consequently,this impairment hindered the bone formation of mesenchymal stem cells,resulting in osteopenia in mice.Mechanically,the impaired property of mesenchymal stem cells which was caused by high salt was controlled by dynamin-related protein 1 mediated mitochondrial fission,which inhibited the classical Wnt signaling pathway.Furthermore,the osteogenic property of mesenchymal stem cells decreased by high salt could be restored by exosomes to transfer the mitochondrial DNA into the impaired mesenchymal stem cells.This study provides not only new strategies for promoting bone regeneration but also new insights into the effect and mechanism of exosome-mediated delivery.

关 键 词：high salt dynamin-related protein 1 mitochondrial injury EXOSOMES bone regeneration 

分 类 号：R68[医药卫生—骨科学]