Extracellular vesicles derived from mesenchymal stem cells containing microRNA-381 protect against spinal cord injury in a rat model via the BRD4/WNT5A axis

Bone & Joint Research

article

Xufeng Jia¹  Guangping Huang¹  Shaohua Wang¹  Miao Long¹  Xiaojun Tang¹  Daxiong Feng²  Qingzhong Zhou² 

[1] The People’s Hospital of Jianyang City;The Affiliated Hospital of Southwest Medical University

关键词: Mesenchymal stem cell;    Extracellular vesicle;    miR-381;    Dorsal root ganglia;    Spinal cord injury;   

DOI  :  10.1302/2046-3758.105.BJR-2020-0020.R1

学科分类：骨科学

来源: British Editorial Society Of Bone And Joint Surgery

【 摘 要 】

AimsNon-coding microRNA (miRNA) in extracellular vesicles (EVs) derived from mesenchymal stem cells (MSCs) may promote neuronal repair after spinal cord injury (SCI). In this paper we report on the effects of MSC-EV-microRNA-381 (miR-381) in a rodent model of SCI.MethodsIn the current study, the luciferase assay confirmed a binding site of bromodomain-containing protein 4 (BRD4) and Wnt family member 5A (WNT5A). Then we detected expression of miR-381, BRD4, and WNT5A in dorsal root ganglia (DRG) cells treated with MSC-isolated EVs and measured neuron apoptosis in culture by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining. A rat model of SCI was established to detect the in vivo effect of miR-381 and MSC-EVs on SCI.ResultsWe confirmed an interaction between miR-381 and BRD4, and showed that miR-381 overexpression inhibited the expression of BRD4 in DRG cells as well as the apoptosis of DRG cells through WNT5A via activation of Ras homologous A (RhoA)/Rho-kinase activity. Moreover, treatment of MSC-EVs rescued neuron apoptosis and promoted the recovery of SCI through inhibition of the BRD4/WNT5A axis.ConclusionTaken altogether, miR-381 derived from MSC-EVs can promote the recovery of SCI through BRD4/WNT5A axis, providing a new perspective on SCI treatment.

【 授权许可】

CC BY-NC