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rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
2010-11-30
pubmed:abstractText
PC-1 is an enzymatic generator of pyrophosphate and a critical regulator of tissue mineralization. We previously showed that fibroblast growth factor-2 (FGF2) specifically induces PC-1 expression in calvarial pre-osteoblasts and that this occurs via a transcriptional mechanism involving Runx2. Because aberrant FGF signaling and Msx2 activity result in similar craniofacial skeletal defects and because Msx2 is an established regulator of osteoblastic gene expression, here we investigate Msx2 as an additional mediator of PC-1 gene expression. mRNA analysis and experiments utilizing PC-1 gene promoter/luciferase reporter constructs demonstrate that Msx2 promotes transcription of the PC-1 gene downstream of FGF2. Results indicate that both Msx2 and Runx2 are recruited to a conserved core Msx2 binding site within the PC-1 gene promoter upon FGF2 stimulation, and that Msx2 and Runx2 function together to induce PC-1 gene expression in osteoblastic cells. Here we show that FGF signaling promotes Msx2 transcriptional activity on the PC-1 gene promoter via the Frs2/MAPK signaling pathway. To our knowledge, this is the first report of Msx2 functioning as a transcriptional enhancer downstream of FGF2 in calvarial pre-osteoblasts. As activating mutations in FGF receptors and Msx2 result in similar craniofacial skeletal disorders, our findings support the idea that FGF signaling and Msx2 activity influence cranial osteogenesis via the same molecular mechanism.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
1097-4644
pubmed:author
pubmed:copyrightInfo
Copyright © 2010 Wiley-Liss, Inc.
pubmed:issnType
Electronic
pubmed:day
1
pubmed:volume
111
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1346-58
pubmed:meshHeading
pubmed:year
2010
pubmed:articleTitle
FGF2 promotes Msx2 stimulated PC-1 expression via Frs2/MAPK signaling.
pubmed:affiliation
Department of Periodontics and Oral Medicine, University of Michigan, Ann Arbor, Michigan 48109-1078, USA.
pubmed:publicationType
Journal Article