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. 2019 Mar;5(1):55-64.
doi: 10.1007/s40610-019-0115-4. Epub 2019 Jan 24.

MICROmanagement of Runx2 Function in Skeletal Cells

Benjamin J Wildman  1 , Tanner C Godfrey  1 , Mohammad Rehan  1 , Yuechuan Chen  1 , Lubana H Afreen  1 , Quamarul Hassan  1
Affiliations

MICROmanagement of Runx2 Function in Skeletal Cells

Benjamin J Wildman et al. Curr Mol Biol Rep. 2019 Mar.

Abstract

Purpose of review-: Precise and temporal expression of Runx2 and its regulatory transcriptional network is a key determinant for the intricate cellular and developmental processes in adult bone tissue formation. This review analyzes how microRNA functions to regulate this network, and how dysregulation results in bone disorders.

Recent findings-: Similar to other biologic processes, microRNA (miRNA/miR) regulation is undeniably indispensable to bone synthesis and maintenance. There exists a miRNA-RUNX2 network where RUNX2 regulates the transcription of miRs, or is post transcriptionally regulated by a class of miRs, forming a variety of miR-RUNX2 regulatory pathways which regulate osteogenesis.

Summary-: The current review provides insights to understand transcriptional-post transcriptional regulatory network governed by Runx2 and osteogenic miRs, and is based largely from in vitro and in vivo studies. When taken together, this article discusses a new regulatory layer of bone tissue specific gene expression by RUNX2 influenced via miRNA.

Keywords: MicroRNA; Noncoding RNA; Osteoblast Differentiation; Osteoblastogenesis; Posttranscriptional Repression; Runx2.

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Conflict of interest statement

Conflict of Interest Benjamin J. Wildman, Tanner C. Godfrey, Mohammad Rehan, Yuechuan Chen, Lubana H. Afreen and Quamarul Hassan each declare that they have no conflicts of interest with the contents of this article.

Figures

Figure 1.
Figure 1.. MiRNA Regulation of Runx2 in Skeletal Cells.
(A) Cellular signaling-miRNAs-Runx2 axis controls osteogenesis. BMP2 signaling increased the expression of miR-3960, miR-2861, which target HoxA2 and Hdac5 (inhibitors of Runx2), however, decreased the expression miR-133, miR-135 and miR-30, which directly target Runx2, Smad1 and Smad5 hence, in multiple way protectedRunx2 function that promote matrix formation and mineralization during osteoblast differentiation. (B, left) Negative regulation by Runx2 of inhibiting miRNAs, miR-23a cluster, miR-665 and miR-31 to relieve the inhibition of Runx2, Satb2, Dlx3 and Kat6a to promote osteoblast, odontoblast and dental follicular cell differentiation. (B, right) Positive regulation by Runx2 of activating miRNAs, miR-3960 and miR-2861which target inhibitors of Runx2, Hdac5, HoxA2; miR-302a targets COUP-TFII, and miR-690 targets p65 generates a feed forward circuit to induce osteogenesis. (C) miRNA-mediated inhibition of Runx2 expression. The illustration of 4 kb Runx2 3′ untranslated region (black solid line). In upper panel, a subset of Runx2-targeting miRNAs (Osteo miRNAome) express in osteoblasts, odontoblasts, bone marrow stromal cells and dental follicular cells at stages of growth and differentiation (blue box) control Runx2 mRNA stability and regulate osteogenesis and alter mesenchymal phenotypes. In lower panel, another subset of miRNAs (Metastasis miRNAome) express in breast, prostate, bone and head and neck cancer cells control Runx2 post transcriptionally to accelerate bone metastasis and osteolysis.
See this image and copyright information in PMC

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