Initiation of Early Osteoblast Differentiation Events through the Direct Transcriptional Regulation of Msx2 by FOXC1

Hierarchal transcriptional regulatory networks function to control the correct spatiotemporal patterning of the mammalian skeletal system. One such factor, the forkhead box transcription factor FOXC1 is necessary for the correct formation of the axial and craniofacial skeleton. Previous studies have...

Full description

Bibliographic Details
Main Authors:	Mirzayans, Farideh, Lavy, Rotem, Penner-Chea, Jonathan, Berry, Fred B.
Format:	Online
Language:	English
Published:	Public Library of Science 2012
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3492307/

id	pubmed-3492307
recordtype	oai_dc
spelling	pubmed-34923072012-11-09 Initiation of Early Osteoblast Differentiation Events through the Direct Transcriptional Regulation of Msx2 by FOXC1 Mirzayans, Farideh Lavy, Rotem Penner-Chea, Jonathan Berry, Fred B. Research Article Hierarchal transcriptional regulatory networks function to control the correct spatiotemporal patterning of the mammalian skeletal system. One such factor, the forkhead box transcription factor FOXC1 is necessary for the correct formation of the axial and craniofacial skeleton. Previous studies have demonstrated that the frontal and parietal bones of the skull fail to develop in mice deficient for Foxc1. Furthermore expression of the Msx2 homeobox gene, an essential regulator of calvarial bone development is absent in the skull mesenchymal progenitors of Foxc1 mutant mice. Thus we sought to determine whether Msx2 was a direct target of FOXC1 transcriptional regulation. Here, we demonstrate that elevated expression of FOXC1 can increase endogenous Msx2 mRNA levels. Chromatin immunoprecipitation experiments reveal that FOXC1 occupies a conserved element in the MSX2 promoter. Using a luciferase reporter assay, we demonstrate that FOXC1 can stimulate the activity of the both human and mouse MSX2 promoters. We also report that reducing FOXC1 levels by RNA interference leads to a decrease in MSX2 expression. Finally, we demonstrate that heterologous expression of Foxc1 in C2C12 cells results in elevated alkaline phosphatase activity and increased expression of Runx2 and Msx2. These data indicate that Foxc1 expression leads to a similar enhanced osteogenic differentiation phenotype as observed with Msx2 overexpression. Together these findings suggest that a Foxc1->Msx2 regulatory network functions in the initial stages of osteoblast differentiation. Public Library of Science 2012-11-07 /pmc/articles/PMC3492307/ /pubmed/23145080 http://dx.doi.org/10.1371/journal.pone.0049095 Text en © 2012 Mirzayans et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Mirzayans, Farideh Lavy, Rotem Penner-Chea, Jonathan Berry, Fred B.
spellingShingle	Mirzayans, Farideh Lavy, Rotem Penner-Chea, Jonathan Berry, Fred B. Initiation of Early Osteoblast Differentiation Events through the Direct Transcriptional Regulation of Msx2 by FOXC1
author_facet	Mirzayans, Farideh Lavy, Rotem Penner-Chea, Jonathan Berry, Fred B.
author_sort	Mirzayans, Farideh
title	Initiation of Early Osteoblast Differentiation Events through the Direct Transcriptional Regulation of Msx2 by FOXC1
title_short	Initiation of Early Osteoblast Differentiation Events through the Direct Transcriptional Regulation of Msx2 by FOXC1
title_full	Initiation of Early Osteoblast Differentiation Events through the Direct Transcriptional Regulation of Msx2 by FOXC1
title_fullStr	Initiation of Early Osteoblast Differentiation Events through the Direct Transcriptional Regulation of Msx2 by FOXC1
title_full_unstemmed	Initiation of Early Osteoblast Differentiation Events through the Direct Transcriptional Regulation of Msx2 by FOXC1
title_sort	initiation of early osteoblast differentiation events through the direct transcriptional regulation of msx2 by foxc1
description	Hierarchal transcriptional regulatory networks function to control the correct spatiotemporal patterning of the mammalian skeletal system. One such factor, the forkhead box transcription factor FOXC1 is necessary for the correct formation of the axial and craniofacial skeleton. Previous studies have demonstrated that the frontal and parietal bones of the skull fail to develop in mice deficient for Foxc1. Furthermore expression of the Msx2 homeobox gene, an essential regulator of calvarial bone development is absent in the skull mesenchymal progenitors of Foxc1 mutant mice. Thus we sought to determine whether Msx2 was a direct target of FOXC1 transcriptional regulation. Here, we demonstrate that elevated expression of FOXC1 can increase endogenous Msx2 mRNA levels. Chromatin immunoprecipitation experiments reveal that FOXC1 occupies a conserved element in the MSX2 promoter. Using a luciferase reporter assay, we demonstrate that FOXC1 can stimulate the activity of the both human and mouse MSX2 promoters. We also report that reducing FOXC1 levels by RNA interference leads to a decrease in MSX2 expression. Finally, we demonstrate that heterologous expression of Foxc1 in C2C12 cells results in elevated alkaline phosphatase activity and increased expression of Runx2 and Msx2. These data indicate that Foxc1 expression leads to a similar enhanced osteogenic differentiation phenotype as observed with Msx2 overexpression. Together these findings suggest that a Foxc1->Msx2 regulatory network functions in the initial stages of osteoblast differentiation.
publisher	Public Library of Science
publishDate	2012
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3492307/
_version_	1611922398581358592

Initiation of Early Osteoblast Differentiation Events through the Direct Transcriptional Regulation of Msx2 by FOXC1

Similar Items