The miR-21-5p enriched in the apoptotic bodies of M2 macrophage-derived extracellular vesicles alleviates osteoarthritis by changing macrophage phenotype

作者全名："Qin, Leilei; Yang, Jianye; Su, Xudong; li, Xilan; Lei, Yiting; Dong, Lili; Chen, Hong; Chen, Cheng; Zhao, Chen; Zhang, Huan; Deng, Jun; Hu, Ning; Huang, Wei"

作者地址："[Qin, Leilei; Yang, Jianye; Su, Xudong; Lei, Yiting; Dong, Lili; Chen, Hong; Chen, Cheng; Zhao, Chen; Zhang, Huan; Hu, Ning; Huang, Wei] Chongqing Med Univ, Affiliated Hosp 1, Dept Orthopaed, Chongqing 400016, Peoples R China; [Qin, Leilei; Yang, Jianye; Su, Xudong; Lei, Yiting; Dong, Lili; Chen, Hong; Chen, Cheng; Zhao, Chen; Zhang, Huan; Hu, Ning; Huang, Wei] Chongqing Med Univ, Orthoped Lab, Affiliated Hosp 1, Chongqing 400016, Peoples R China; [li, Xilan; Deng, Jun] Army Med Univ, Southwest Hosp, Inst Burn Res, State Key Lab Trauma Burn & Combined Injury, Chongqing 400038, Peoples R China"

通信作者："Hu, N; Huang, W (通讯作者)，Chongqing Med Univ, Affiliated Hosp 1, Dept Orthopaed, Chongqing 400016, Peoples R China.; Hu, N; Huang, W (通讯作者)，Chongqing Med Univ, Orthoped Lab, Affiliated Hosp 1, Chongqing 400016, Peoples R China.; Deng, J (通讯作者)，Army Med Univ, Southwest Hosp, Inst Burn Res, State Key Lab Trauma Burn & Combined Injury, Chongqing 400038, Peoples R China."

来源：GENES & DISEASES

ESI学科分类：MOLECULAR BIOLOGY & GENETICS

WOS号：WOS:001015086800001

JCR分区：Q1

影响因子：6.8

年份：2023

卷号：10

期号：3

开始页：1114

结束页：1129

文献类型：Article

关键词：Apoptotic body; Extracellular vesicles; Macrophage phenotype switch; MicroRNA-21; Osteoarthritis

摘要："Macrophages (M4s) play a crucial role in the pathological progression of osteoar-thritis (OA) by regulating inflammation and tissue repair. Decreasing pro-inflammatory M1-M4s and increasing anti-inflammatory M2-M4s can alleviate OA-related inflammation and pro-mote cartilage repair. Apoptosis is a natural process associated with tissue repair. A large num-ber of apoptotic bodies (ABs), a type of extracellular vesicle, are produced during apoptosis, and this is associated with a reduction in inflammation. However, the functions of apoptotic bodies remain largely unknown. In this study, we investigated the role of M2-M4s-derived apoptotic bodies (M2-ABs) in regulating the M1/M2 balance of macrophages in a mouse model of OA. Our data show that M2-ABs can be targeted for uptake by M1-M9s, and this reprograms M1-to-M2 phenotypes within 24 h. The M2-ABs significantly ameliorated the severity of OA, alleviated the M1-mediated pro-inflammatory environment, and inhibited chondrocyte apoptosis in mice. RNA-seq revealed that M2-ABs were enriched with miR-21-5p, a microRNA that is negatively correlated with articular cartilage degeneration. Inhibiting the function of miR-21-5p in M1-M9s significantly reduced M2-ABs-guided M1-to-M2 reprogramming following in vitro cell transfection. Together, these results suggest that M2-derived apoptotic bodies can prevent articular cartilage damage and improve gait abnormalities in OA mice by reversing the inflammatory response caused by M1 macrophages. The mechanism underlying these findings may be related to miR-21-5p-regulated inhibition of inflammatory factors. The application of M2-ABs may represent a novel cell therapy, and could provide a valuable strategy for the treatment of OA and/or chronic inflammation. 2022 The Authors. Publishing services by Elsevier B.V. on behalf of KeAi Communications Co., Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons. org/licenses/by-nc-nd/4.0/)."

基金机构："National Natural Science Foundation of China [81972069, 82072443]"

基金资助正文：Funding This work was supported by the National Natural Science Foundation of China (No. 81972069 and 82072443) .