title: Overexpression of microRNA-124 promotes the neuronal differentiation of bone marrow-derived mesenchymal stem cells.
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.
authors.affiliation: Department of Orthopedics, First Affiliated Hospital of China Medical University, Shenyang, Liaoning Province, China.
authors.forename: Defeng
authors.initials: D
authors.lastname: Zou
authors.affiliation: Department of Orthopedics, Jinhua Central Hospital of Zhejiang University, Jinhua, Zhejiang Province, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Orthopedics, First Affiliated Hospital of China Medical University, Shenyang, Liaoning Province, China.
authors.forename: Yaxin
authors.initials: Y
authors.lastname: Han
authors.affiliation: Department of Orthopedics, First Affiliated Hospital of China Medical University, Shenyang, Liaoning Province, China.
authors.forename: Chen
authors.initials: C
authors.lastname: Lv
authors.affiliation: Department of Orthopedics, First Affiliated Hospital of China Medical University, Shenyang, Liaoning Province, China.
authors.forename: Guanjun
authors.initials: G
authors.lastname: Tu
keywords: GeneChip; NSFC grant; bone marrow-derived mesenchymal stem cells; lentivirus; microRNA-124; motor function; nerve regeneration; neural regeneration; neural stem cells; neurogenesis; overexpression; spinal cord injury