Li Dailong, Xie Xuyuan, Ou Yuxuan, Sun Peiwen, Lin Jiezhao, Yu Cheng, Huang Haoran, Huang Longcheng, Yang Changjian, Kuang Wenhao, Zhou Chusong
Department of Spinal Surgery, Orthopedic Center, Zhujiang Hospital, Southern Medical University, Guangzhou, 510280, China.
Department of Spinal Surgery, Orthopedic Center, Zhujiang Hospital, Southern Medical University, Guangzhou, 510280, China; Department of Orthopedics, The First People's Hospital of Zhaoqing, Zhaoqing, 526000, China.
Arch Biochem Biophys. 2025 Jul;769:110434. doi: 10.1016/j.abb.2025.110434. Epub 2025 Apr 22.
Spinal cord injury (SCI) is a very harmful neurological disease that can cause serious damage to sensation, movement, and autonomic nervous function below the affected area. Apoptosis and inflammatory response play important roles in the pathological process of spinal cord injury. The exosomes secreted by bone marrow mesenchymal stem cells (BMSCs) may play a protective role against spinal cord injury. However, the detailed mechanism behind this is not fully understood. The main objective of this study was to investigate the anti-inflammatory and anti-apoptotic effects of bone marrow mesenchymal stem cell exosomes (BMSCs-EXO) in SCI in vitro and in vivo and their mechanisms. The study demonstrated that bone marrow mesenchymal stem cells reduced apoptosis and inflammation and promoted axon growth in LPS-treated PC12 cells. The miRDB predicted that miR-24-3p targets MAPK9(JNK2). Transcriptome sequencing and Western blot confirmed that miR-24-3p inhibits the JNK/c-Jun/c-Fos pathway by targeting MAPK9. In vivo experiments, injection of BMSC exosomes overexpressing miR-24-3p from the tail vein attenuated the SCI exercise injury-related behavior in rats. In conclusion, this study indicates that bone marrow MSC-derived exosomes can mitigate SCI-related injury by suppressing apoptosis and inflammation, with miR-24-3p playing a crucial role, potentially offering a novel therapeutic approach for SCI treatment.
脊髓损伤（SCI）是一种极具危害性的神经系统疾病，可对损伤部位以下的感觉、运动及自主神经功能造成严重损害。细胞凋亡和炎症反应在脊髓损伤的病理过程中发挥着重要作用。骨髓间充质干细胞（BMSCs）分泌的外泌体可能对脊髓损伤起到保护作用。然而，其背后的详细机制尚未完全明确。本研究的主要目的是探究骨髓间充质干细胞外泌体（BMSCs-EXO）在体外和体内对脊髓损伤的抗炎和抗凋亡作用及其机制。研究表明，骨髓间充质干细胞可减少脂多糖处理的PC12细胞的凋亡和炎症，并促进轴突生长。miRDB预测miR-24-3p靶向MAPK9（JNK2）。转录组测序和蛋白质印迹证实，miR-24-3p通过靶向MAPK9抑制JNK/c-Jun/c-Fos通路。在体内实验中，经尾静脉注射过表达miR-24-3p的骨髓间充质干细胞外泌体可减轻大鼠脊髓损伤运动损伤相关行为。总之，本研究表明，骨髓间充质干细胞来源的外泌体可通过抑制细胞凋亡和炎症来减轻脊髓损伤相关损伤，miR-24-3p发挥关键作用，可能为脊髓损伤治疗提供一种新的治疗方法。
