Open AccessExtracellular vesicles derived from mesenchymal stem cells containing microRNA-381 protect against spinal cord injury in a rat model via the BRD4/WNT5A axis
Author(s) -
Xufeng Jia,
Guangping Huang,
Shaohua Wang,
Long Miao,
Xiaojun Tang,
Daxiong Feng,
Qiang Zhou
Publication year - 2021
Publication title -
bone and joint research
Language(s) - English
Resource type - Journals
ISSN - 2046-3758
DOI - 10.1302/2046-3758.105.bjr-2020-0020.r1
Subject(s) - mesenchymal stem cell , microbiology and biotechnology , terminal deoxynucleotidyl transferase , microrna , tunel assay , wnt signaling pathway , apoptosis , spinal cord injury , chemistry , biology , spinal cord , signal transduction , biochemistry , neuroscience , gene
Aims Non-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.Methods In 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.Results We 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.Conclusion Taken altogether, miR-381 derived from MSC-EVs can promote the recovery of SCI through BRD4/WNT5A axis, providing a new perspective on SCI treatment. Cite this article: Bone Joint Res 2021;10(5):328–339.