title: Epigenetic silencing of HDAC1 by miR-449a upregulates Runx2 and promotes osteoblast differentiation.
abstract: Human-induced pluripotent (iPS) cells can be induced to differentiate into osteoblasts, but the process is inefficient and time-consuming. Previous studies indicated a close association between the expression of Runx2 and osteoblast differentiation, and established that the transcriptional activation of the Runx2 gene was closely associated with histone acetylation. microRNA-449a (miR-449a) represses HDAC1 expression, thereby regulating histone acetylation. In the present study, whether the expression of miR-449a enhanced the generation of osteoblasts from human iPS cells was investigated. Introduction of miR-449a into human iPS cells resulted in the expression of osteoblast markers after only four days, compared to eight days for untransfected human iPS cells. Differentiation to osteoblasts was associated with a reduction in HDAC1 expression, and higher levels of histone acetylation, particularly at the binding sites on the Runx2 promoter in the human miR-449a-transfected iPS cells. Silencing of endogenous HDAC1 expression by exogenous miR-449a therefore maintains histone acetylation status, stimulates Runx2 gene expression and rapidly promotes osteoblast differentiation.
authors.affiliation: Shanghai Tenth People's Hospital, Medical School, Tongji University, Shanghai 200072, P.R. China.
authors.forename: Te
authors.initials: T
authors.lastname: Liu
authors.affiliation: Shanghai Tenth People's Hospital, Medical School, Tongji University, Shanghai 200072, P.R. China.
authors.forename: Lengchen
authors.initials: L
authors.lastname: Hou
authors.affiliation: The Affiliated Stomatology Hospital of Tongji University, Shanghai 200072, P.R. China.
authors.forename: Yanhui
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Laboratoire PROTEE, Bâtiment R, Université du Sud Toulon‑Var, 83957 La Garde Cedex, France.
authors.forename: Yongyi
authors.initials: Y
authors.lastname: Huang
mesh_terms: D020413:3' Untranslated Regions; D001483:Base Sequence; D001665:Binding Sites; D015415:Biomarkers; D002454:Cell Differentiation / Q000235:genetics*; D042002:Chromatin Assembly and Disassembly; D050659:Core Binding Factor Alpha 1 Subunit / Q000235:genetics*; D042783:Endothelial Cells; D044127:Epigenesis, Genetic; D005260:Female; D005786:Gene Expression Regulation; D020868:Gene Silencing; D056284:Histone Deacetylase 1 / Q000737:chemistry / Q000235:genetics*; D006801:Humans; D035683:MicroRNAs / Q000737:chemistry / Q000235:genetics*; D010006:Osteoblasts / Q000166:cytology* / Q000378:metabolism*; D011247:Pregnancy; D014158:Transcription, Genetic; D014162:Transfection
chemical_list: D020413:3' Untranslated Regions; D015415:Biomarkers; D050659:Core Binding Factor Alpha 1 Subunit; C544530:MIRN449 microRNA, human; D035683:MicroRNAs; C110550:HDAC1 protein, human; D056284:Histone Deacetylase 1