Small extracellular vesicles derived from hypoxic preconditioned dental pulp stem cells ameliorate inflammatory osteolysis by modulating macrophage polarization and osteoclastogenesis  

作　　者：Jun Tian Weiyang Chen Yuhua Xiong Qianer Li Siyi Kong Mengjie Li Chunfeng Pang Yu Qiu Zhezhen Xu Qimei Gong Xi Wei 

机构地区：[1]Hospital of Stomatology,Guanghua School of Stomatology,Sun Yat-Sen University,Guangzhou,Guangdong,510055,PR China [2]Guangdong Provincial Key Laboratory of Stomatology,Guangzhou,Guangdong,510055,PR China

出　　处：《Bioactive Materials》2023年第4期326-342,共17页生物活性材料（英文）

基　　金：This work was supported by National Natural Science Foundation of China(No.81870750,81970925,81900994);the Guangdong Financial Fund for High-Caliber Hospital Construction(174-2018-XMZC-0001-03-0125/D-08).

摘　　要：Extensive macrophage inflammatory responses and osteoclast formation are predominant during inflammatory or infective osteolysis.Mesenchymal stem cell(MSC)-derived small extracellular vesicles(MSC-sEV)have been shown to exert therapeutic effects on bone defects.However,cultured MSCs are typically exposed to normoxia(21%O2)in vitro,which differs largely from the oxygen concentration in vivo under hypoxic conditions.It is largely unknown whether sEV derived from dental pulp stem cells(DPSCs)cultured under hypoxic conditions(Hypo-sEV)exert better therapeutic effects on lipopolysaccharide(LPS)-induced inflammatory osteolysis than those cultured under normoxic conditions(Nor-sEV)by simultaneously inhibiting the macrophage inflammatory response and osteoclastogenesis.In this study,we show that hypoxia significantly induces the release of sEV from DPSCs.Moreover,Hypo-sEV exhibit significantly improved efficacy in promoting M2 macrophage polarization and suppressing osteoclast formation to alleviate LPS-induced inflammatory calvarial bone loss compared with Nor-sEV.Mechanistically,hypoxia preconditioning markedly alters the miRNA profiles of DPSC-sEV.MiR-210-3p is enriched in Hypo-sEV,and can simultaneously induce M2 macrophage generation and inhibit osteoclastogenesis by targeting NF-κB1 p105,which attenuates osteolysis.Our study suggests a promising potential for hypoxia-induced DPSC-sEV to treat inflammatory or infective osteolysis and identifies a novel role of miR-210-3p in concurrently hindering osteoclastogenesis and macrophage inflammatory response by inhibiting NF-kB1 expression.

关 键 词：Dental pulp stem cells Small extracellular vesicles Macrophage OSTEOCLAST Inflammatory osteolysis 

分 类 号：R318[医药卫生—生物医学工程]