MicroRNA miR-378 promotes BMP2-induced osteogenic differentiation of mesenchymal progenitor cells

Marlinda Hupkes,Everardus J van Zoelen,Koen J Dechering,Ana M Sotoca,José M Hendriks

doi:10.1186/1471-2199-15-1

Abstract

BackgroundMicroRNAs (miRNAs) are a family of small, non-coding single-stranded RNA molecules involved in post-transcriptional regulation of gene expression. As such, they are believed to play a role in regulating the step-wise changes in gene expression patterns that occur during cell fate specification of multipotent stem cells. Here, we have studied whether terminal differentiation of C2C12 myoblasts is indeed controlled by lineage-specific changes in miRNA expression.ResultsUsing a previously generated RNA polymerase II (Pol-II) ChIP-on-chip dataset, we show differential Pol-II occupancy at the promoter regions of six miRNAs during C2C12 myogenic versus BMP2-induced osteogenic differentiation. Overexpression of one of these miRNAs, miR-378, enhances Alp activity, calcium deposition and mRNA expression of osteogenic marker genes in the presence of BMP2.ConclusionsOur results demonstrate a previously unknown role for miR-378 in promoting BMP2-induced osteogenic differentiation.

Highlights

MicroRNAs are a family of small, non-coding single-stranded RNA molecules involved in post-transcriptional regulation of gene expression
C2C12 lineage-specific miRNA expression To identify miRNAs that are differentially expressed during C2C12 myogenic versus bone morphogenetic protein 2 (BMP2)-induced osteogenic differentiation, and thereby might play a role in lineage restriction, we made use of our previously generated polymerase II (Pol-II) ChIP-on-chip dataset [27]
This dataset contains Pol-II occupancy data for undifferentiated C2C12 cells (d0) and cells treated with or without BMP2 for 1, 3 and 6 days, whereby changes in Pol-II occupancy are considered to reflect changes in transcriptional activity

Summary

Introduction

MicroRNAs (miRNAs) are a family of small, non-coding single-stranded RNA molecules involved in post-transcriptional regulation of gene expression. The generation of distinct populations of terminally differentiated, mature specialized cell types from multipotent stem cells, via progenitor cells, is characterized by a progressive restriction of differentiation potential that involves a tightly controlled, coordinated activation and repression of specific subsets of genes. This process depends on the orchestrated action of key regulatory transcription factors in combination with changes in epigenetic modifications that regulate which regions in the genome are accessible for transcription [1]. The strand that is incorporated into RISC with lowest efficiency is referred to with an asterisk (miRNA*) and, since non-incorporated strands are thought to be degraded, is less-abundant than its counterpart [12]

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Conclusion