PMID- 31626878 OWN - NLM STAT- MEDLINE DCOM- 20210104 LR - 20210104 IS - 1872-7972 (Electronic) IS - 0304-3940 (Linking) VI - 714 DP - 2020 Jan 1 TI - Suppression of miR-10a-5p in bone marrow mesenchymal stem cells enhances the therapeutic effect on spinal cord injury via BDNF. PG - 134562 LID - S0304-3940(19)30665-2 [pii] LID - 10.1016/j.neulet.2019.134562 [doi] AB - BACKGROUNDS/AIMS: Brain-derived neurotrophic factor (BDNF) plays a primary role in the maturation, proliferation, and differentiation of neuronal cells, can induce bone-marrow-derived mesenchymal stem cells (MSCs) to differentiate into nerve cells. This study aims to explore whether regulation of BDNF through microRNAs (miRNAs) in MSCs may further enhance the therapeutic effect on spinal cord injury (SCI). METHODS: Bioinformatics analyses were done to predict miRNAs that target BDNF in MSCs. Dual-luciferase reporter gene assays were performed to verify the target relationship between microRNA and BDNF. We examined the mRNA and protein levels of BDNF in MSCs by RT-qPCR and Western blot, respectively. CCK 8 assay was chosen to assess cell viability. MSCs were transduced with miR-10a-5p-ASO, which were transplanted into rats that underwent SCI. The tissue integrity percentage, cavity volume, and Basso-Beattie-Bresnahan (BBB) scale were assessed. Neurofilament (NF) was detected using immunohistochemistry. Histological features of spinal cord tissues examined following HE staining. RESULTS: MiR-10a-5p inhibited protein translation of BDNF, through binding to the 3'-UTR of the BDNF. MSCs transduced with MiR-10a-5p-ASO further increased the tissue integrity percentage, decreased cavity volume, and enhanced the recovery of BBB score in SCI model rats, compared to control MSCs. CONCLUSION: Upregulation of BDNF by miR-10a-5p suppression in MSCs further improve the therapeutic potential of MSCs in treating SCI in rats. CI - Copyright (c) 2019. Published by Elsevier B.V. FAU - Zhang, Tongxia AU - Zhang T AD - Department of Neurology, Research Institute of Neuromuscular and Neurodegenerative Diseases, Qilu Hospital of Shandong University, Jinan, 250012, China. FAU - Liu, Chong AU - Liu C AD - Department of Neurosurgery, Qilu Hospital of Shandong University and Institute of Brain and Brain-Inspired Science, Shandong University, Jinan, 250012, China. FAU - Chi, Lingyi AU - Chi L AD - Department of Neurosurgery, Qilu Hospital of Shandong University and Institute of Brain and Brain-Inspired Science, Shandong University, Jinan, 250012, China. Electronic address: chilingyi@163.com. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20191015 PL - Ireland TA - Neurosci Lett JT - Neuroscience letters JID - 7600130 RN - 0 (3' Untranslated Regions) RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (MIRN10 microRNA, rat) RN - 0 (MicroRNAs) RN - 0 (Oligonucleotides, Antisense) SB - IM MH - 3' Untranslated Regions MH - Animals MH - Bone Marrow Cells MH - Brain-Derived Neurotrophic Factor/*genetics/metabolism MH - Cell Differentiation MH - Cell Proliferation/drug effects/*genetics MH - Male MH - Mesenchymal Stem Cell Transplantation MH - Mesenchymal Stem Cells/drug effects/*metabolism MH - MicroRNAs/antagonists & inhibitors/*metabolism MH - Neurogenesis/drug effects/*genetics MH - Oligonucleotides, Antisense/pharmacology MH - Protein Biosynthesis MH - Rats MH - Spinal Cord Injuries/metabolism/pathology/*therapy MH - Up-Regulation OTO - NOTNLM OT - BDNF OT - Bone marrow mesenchymal stem cells OT - Spinal cord injury OT - miR-10a-5p EDAT- 2019/10/19 06:00 MHDA- 2021/01/05 06:00 CRDT- 2019/10/19 06:00 PHST- 2019/06/20 00:00 [received] PHST- 2019/09/28 00:00 [revised] PHST- 2019/10/14 00:00 [accepted] PHST- 2019/10/19 06:00 [pubmed] PHST- 2021/01/05 06:00 [medline] PHST- 2019/10/19 06:00 [entrez] AID - S0304-3940(19)30665-2 [pii] AID - 10.1016/j.neulet.2019.134562 [doi] PST - ppublish SO - Neurosci Lett. 2020 Jan 1;714:134562. doi: 10.1016/j.neulet.2019.134562. Epub 2019 Oct 15.