Linked Life Data

16707491

Source:http://linkedlifedata.com/resource/pubmed/id/16707491

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
29
pubmed:dateCreated
2006-7-17
pubmed:abstractText
Bone remodeling depends upon proper osteoblast and osteoclast function. Bone morphogenetic protein-2 (BMP-2) stimulates differentiation of osteoblasts from pluripotent precursors. Osteoclast formation depends on the concerted action of osteoblast-derived receptor activator of NF-kappaB ligand and colony-stimulating factor-1 (CSF-1). BMP-2 stimulates receptor activator of NF-kappaB ligand expression. However, the effect of BMP-2 on CSF-1 expression has not been studied. We investigated the role of BMP-2 in CSF-1 expression in osteogenic C2C12 cells. Incubation of C2C12 cells with BMP-2 supported osteoclastogenesis of spleen cells with a concomitant increase in expression of CSF-1 mRNA and protein. To determine the mechanism, we identified a BMP-responsive element between -627 bp and -509 bp in the CSF-1 promoter. DNase I footprint analysis revealed the presence of consensus Smad binding motif in this region. Electrophoretic mobility shift assay showed BMP-2-stimulated binding of proteins to this motif. Mutation of core sequence as well as its 5'- and 3'-flanking sequences abolished the DNA-protein interaction resulting in inhibition of CSF-1 transcription. Supershift analysis detects the presence of Smads 1, 5, and 4 and the transcriptional coactivator CREB-binding protein in the BMP-responsive element-protein complex. In addition, Smads 1 and 5 alone or in combination with Smad 4 increased CSF-1 transcription. Furthermore, CREB-binding protein markedly increased transcription of CSF-1. These data represent the first evidence that BMP-2 increases the osteoclastogenic CSF-1 expression by a transcriptional mechanism using the canonical Smad pathway and provide a mechanism for BMP-2-induced osteoclast differentiation.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
21
pubmed:volume
281
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
20160-70
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed-meshheading:16707491-Animals, pubmed-meshheading:16707491-Bone Morphogenetic Protein 2, pubmed-meshheading:16707491-Bone Morphogenetic Proteins, pubmed-meshheading:16707491-CREB-Binding Protein, pubmed-meshheading:16707491-Cell Differentiation, pubmed-meshheading:16707491-Cell Line, pubmed-meshheading:16707491-Gene Expression Regulation, pubmed-meshheading:16707491-Macrophage Colony-Stimulating Factor, pubmed-meshheading:16707491-Mice, pubmed-meshheading:16707491-Muscle Cells, pubmed-meshheading:16707491-Osteoblasts, pubmed-meshheading:16707491-Osteoclasts, pubmed-meshheading:16707491-Promoter Regions, Genetic, pubmed-meshheading:16707491-Recombinant Proteins, pubmed-meshheading:16707491-Signal Transduction, pubmed-meshheading:16707491-Smad Proteins, pubmed-meshheading:16707491-Transcription, Genetic, pubmed-meshheading:16707491-Transforming Growth Factor beta
pubmed:year
2006
pubmed:articleTitle
Concerted action of Smad and CREB-binding protein regulates bone morphogenetic protein-2-stimulated osteoblastic colony-stimulating factor-1 expression.
pubmed:affiliation
Department of Pathology, University of Texas Health Science Center, San Antonio, TX 78229, USA. choudhury@uthscsa.edu
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, Non-P.H.S., Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural