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Overexpression of microRNA-124 promotes the neuronal differentiation of bone marrow-derived mesenchymal stem cells
Authors:Defeng Zou,  Yi Chen,  Yaxin Han,  Chen Lv,  Guanjun Tu
Affiliation:[1]Department of Orthopedics, First Affiliated Hospital of China Medical University, Shenyang, Liaoning Province, China; [2]Department of Orthopedics, ]inhua Central Hospital of Zhejiang University, ]inhua, Zhejiang Province, China
Abstract:microRNAs (miRNAs) play an important regulatory role in the self-renewal and differentiation of stem cells. In this study, we examined the effects of miRNA-124 (miR-124) overexpression in bone marrow-derived mesenchymal stem cells. In particular, we focused on the effect of overexpression on the differentiation of bone marrow-derived mesenchymal stem cells into neurons. First, we used GeneChip technology to analyze the expression of miRNAs in bone marrow-derived mesenchymal stem cells, neural stem cells and neurons. miR-124 expression was substantially reduced in bone marrow-derived mesenchymal stem cells compared with the other cell types. We constructed a lentiviral vector overexpressing miR-124 and transfected it into bone marrow-derived mesenchymal stem cells. Intracellular expression levels of the neuronal early markers β-III tubulin and microtubule-associated protein-2 were significantly increased, and apoptosis induced by oxygen and glucose deprivation was reduced in transfected cells. After miR-124-transfected bone marrow-derived mesenchymal stem cells were transplanted into the injured rat spinal cord, a large number of cells positive for the neuronal marker neurofilament-200 were observed in the transplanted region. The Basso-Beattie-Bresnahan locomotion scores showed that the motor function of the hind limb of rats with spinal cord injury was substantially improved. These results suggest that miR-124 plays an important role in the differentiation of bone marrow-derived mesenchymal stem cells into neurons. Our findings should facilitate the development of novel strategies for enhancing the therapeutic efficacy of bone marrow-derived mesenchymal stem cell transplantation for spinal cord injury.
Keywords:nerve regeneration  microRNA-124  lentivirus  overexpression  bone marrow-de-rived mesenchymal stem cells  neural stern cells  spinal cord injury  neurogenesis  GeneChip  motor function  NSFC grant  neural regeneration
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