title: MiR-124 inhibits myogenic differentiation of mesenchymal stem cells via targeting Dlx5.
abstract: MicroRNAs (miRNAs), including miR-1, miR-133, and miR-206, play a crucial role in muscle development by regulating muscle cell proliferation and differentiation. The aim of the present study was to define the effect of miR-124 on myogenic differentiation of mesenchymal stem cells (MSCs). The expression level of miR-124 in skeletal muscles was much lower than those in primary cultured bone marrow-derived MSCs and the bone, fat and brain tissues obtained from C57BL/6 mice. Myogenic stimuli significantly decreased the expression levels of miR-124 in mouse bone marrow-derived MSCs and C2C12 cells. Forced expression of miR-124 suppressed the expression of myogenic marker genes such as Myf5, Myod1, myogenin and myosin heavy chain and multinucleated myotube formation. Blockade of endogenous miR-124 with a hairpin inhibitor enhanced myogenic marker gene expression and myotube formation. During myogenic differentiation of MSCs and C2C12 cells, the levels of Dlx5, a known target of miR-124, were inversely regulated with those of miR-124. Furthermore, overexpression of Dlx5 increased myogenic differentiation, whereas knockdown of Dlx5 using siRNA inhibited myogenesis in C2C12 cells. These results suggest that miR-124 is a negative regulator of myogenic differentiation of MSCs and that upregulation of Dlx5 accompanied with downregulation of miR-124 by myogenic stimuli is necessary for the proper progression of myogenic differentiation.
authors.affiliation: Department of Molecular Genetics, School of Dentistry and Dental Research Institute, Seoul National University, Seoul, Korea.
authors.forename: Abdul S
authors.initials: AS
authors.lastname: Qadir
authors.forename: Kyung Mi
authors.initials: KM
authors.lastname: Woo
authors.forename: Hyun-Mo
authors.initials: HM
authors.lastname: Ryoo
authors.forename: TacGhee
authors.initials: T
authors.lastname: Yi
authors.forename: Sun U
authors.initials: SU
authors.lastname: Song
authors.forename: Jeong-Hwa
authors.initials: JH
authors.lastname: Baek
mesh_terms: D000818:Animals; D018929:Cell Culture Techniques; D002454:Cell Differentiation; D002478:Cells, Cultured; D005269:Femur / Q000166:cytology*; D018398:Homeodomain Proteins / Q000235:genetics*; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000235:genetics*; D024510:Muscle Development; D013977:Tibia / Q000166:cytology*
chemical_list: C501120:Dlx5 protein, mouse; D018398:Homeodomain Proteins; D035683:MicroRNAs; C540079:Mirn124 microRNA, mouse
keywords: Dlx5; MESENCHYMAL STEM CELLS; MYOGENESIS; miR-124