M2 exosomes modified by hydrogen sulfide promoted bone regeneration by moesin mediated endocytosis  

作　　者：Yi-kun Zhou Chun-shan Han Zi-lu Zhu Peng Chen Yi-ming Wang Shuai Lin Liu-jing Chen Zi-meng Zhuang Yan-heng Zhou Rui-li Yang 

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

出　　处：《Bioactive Materials》2024年第1期192-205,共14页生物活性材料（英文）

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.Y);Ten-thousand Talents Program QNBJ-2020(R.Y).

摘　　要：Bone defects caused by trauma or tumor led to high medical costs and poor life quality for patients.The exosomes,micro vesicles of 30-150 nm in diameter,derived from macrophages manipulated bone regeneration.However,the role of hydrogen sulfide(H2S)in the biogenesis and function of exosomes and its effects on bone regeneration remains elusive.In this study,we used H2S slow releasing donor GYY4137 to stimulate macrophages and found that H2S promoted the polarization of M2 macrophages to increase bone regeneration of MSCs in vitro and in vivo.Moreover,we developed the H2S pre-treated M2 macrophage exosomes and found these exosomes displayed significantly higher capacity to promote bone regeneration in calvarial bone defects by re-establishing the local immune microenvironment.Mechanically,H2S treatment altered the protein profile of exosomes derived from M2 macrophages.One of the significantly enriched exosomal proteins stimulated by H2S,moesin protein,facilitated the exosomes endocytosis into MSCs,leading to activated theβ-catenin signaling pathway to promote osteogenic differentiation of MSCs.In summary,H2S pretreated M2 exosomes promoted the bone regeneration of MSCs via facilitating exosomes uptake by MSCs and activateβ-catenin signaling pathway.This study not only provides new strategies for promoting bone regeneration,but also provides new insights for the effect and mechanism of exosomes internalization.

关 键 词：MACROPHAGES EXOSOMES Bone regeneration Stem cells Hydrogen sulfide MOESIN 

分 类 号：R318[医药卫生—生物医学工程]