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.

journal_name

Int J Mol Med

authors

Liu T,Hou L,Zhao Y,Huang Y

doi

10.3892/ijmm.2014.2004

subject

Has Abstract

pub_date

2015-01-01 00:00:00

pages

238-46

issue

1

eissn

1107-3756

issn

1791-244X

journal_volume

35

pub_type

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