Bone marrow mesenchymal stem cells-derived exosomal miR-24–3p alleviates spinal cord injury by targeting MAPK9 to inhibit the JNK/c-Jun/c-Fos pathway
Dongzi Li, Xuyuan Xie, Yuxuan Ou, Peiwen Sun, Jiezhao Lin, Yu Cheng, Haoran Huang, Longcheng Huang, Changjian Yang, Wenhao Kuang, Chusong Zhou
Abstract
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.