Apoptotic extracellular vesicles restore homeostasis of the articular microenvironment for the treatment of rheumatoid arthritis  

作　　者：Xian Li Shichun Li Xiaoling Fu Yingjun Wang 

机构地区：[1]School of Materials Science and Engineering,South China University of Technology,Guangzhou,510641,China [2]School of Biomedical Sciences and Engineering,South China University of Technology,Guangzhou International Campus,Guangzhou,511442,China [3]National Engineering Research Center for Tissue Restoration and Reconstruction and Innovation Center for Tissue Restoration and Reconstruction,Guangzhou,510006,China [4]Key Laboratory of Biomedical Engineering of Guangdong Province,South China University of Technology,Guangzhou,510006,China [5]NMPA Key Laboratory for Research and Evaluation of Innovative Biomaterials for Medical Devices,Guangzhou,510700,China

出　　处：《Bioactive Materials》2024年第5期564-576,共13页生物活性材料（英文）

基　　金：supported by the National Natural Science Foundation of China(T2288101,31971266,82272152,U1801252);Guangdong Basic and Applied Basic Research Foundation(2022A1515011925);Science and Technology Program of Guangzhou(202206040001);the Key Research and Development Program of Guangzhou(202007020002).

摘　　要：Rheumatoid arthritis(RA)is a severe autoimmune disease with symptoms including synovial inflammation,cartilage erosion,and bone loss in RA lesions,which eventually lead to joint deformity and function loss.Most current treatments fail to achieve satisfying therapeutic outcomes with some adverse effects.Extracellular vesicles derived from apoptotic cells(apoEVs)have emerged as important mediators in intercellular communication regulating diverse physiological and pathological processes.In this study,we investigated the therapeutic efficacy of macrophage-derived and osteoclast-derived apoEVs(Mφ-apoEVs and OC-apoEVs)on RA.The in vitro results showed that both Mφ-apoEVs and OC-apoEVs induced macrophage repolarization toward the anti-inflammatory M2 phenotype,promoted chondrocyte functions and chondrogenesis,and inhibited osteoclast formation and maturation.In addition,OC-apoEVs promoted osteogenic differentiation.The in vivo study on the CIA mouse model further demonstrated that apoEVs could couple various functions and exert synergistic effects on the joint with RA,as evidenced by the regression of synovial inflammation,the reversal of cartilage damage and bone erosion,and the preservation of joint structure.These findings demonstrated that Mφ-apoEVs and OC-apoEVs contributed to restoring the homeostasis of the overall microenvironment in the RA joint and highlighted their potential application as a promising alternative to treat RA.

关 键 词：Apoptotic extracellular vesicles Microenvironment homeostasis Rheumatoid arthritis 

分 类 号：R593.22[医药卫生—内科学]