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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2001-1-26
pubmed:abstractText
The runt family transcription factor (AML-3/PEBP2alphaA1/Cbfa1/RUNX2) plays a crucial role in formation of the mineralized skeleton during embryogenesis and regulates maturation of the osteoblast phenotype. Because steroid hormones and growth factors significantly influence growth and differentiation properties of osteoblasts, we addressed Cbfa1 as a target gene for regulation by dexamethasone (Dex), 1,25(OH)D(3) (vitamin D(3)), 17beta-estradiol, and transforming growth factor-beta1 (TGF-beta1). The representation of functional protein levels by Western blot analyses and gel mobility shift assays was examined during the growth and mineralization of several conditionally immortalized human osteoblast cell lines HOB 04-T8, 03-CE6, and 03-CE10, each representing different stages of maturation. In situ immunofluorescence demonstrates Cbfa1 is associated with nuclear matrix in punctate domains, some of which are transcriptionally active, colocalizing with phosphorylated RNA polymerase II. Although each of the cell lines exhibited different responses to the steroid hormones and to TGF-beta1, all cell lines showed a similar increase in Cbfa1 protein and DNA binding activity induced only by Dex. On the other hand, Cbfa1 mRNA levels were not altered by Dex treatment. This regulation of Cbfa1 by steroid hormones in human osteoblasts contrasts to modifications in Cbfa1 expression in primary rat calvarial osteoblasts and the mouse MC3T3-E1 osteoblast cell line. Thus, these results reveal multiple levels of regulation of Cbfa1 expression and activity in osteoblasts. Moreover, the data suggest that in committed human osteoblasts, constitutive expression of Cbfa1 may be required to sustain the osteoblast phenotype.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:issn
0730-2312
pubmed:author
pubmed:copyrightInfo
Copyright 2001 Wiley-Liss, Inc.
pubmed:issnType
Print
pubmed:volume
80
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
424-40
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
2001
pubmed:articleTitle
Expression and regulation of Runx2/Cbfa1 and osteoblast phenotypic markers during the growth and differentiation of human osteoblasts.
pubmed:affiliation
Department of Cell Biology, University of Massachusetts Medical School, Worcester, Massachusetts 01655, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't