Linked Life Data

21335072

Source:http://linkedlifedata.com/resource/pubmed/id/21335072

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1-2
pubmed:dateCreated
2011-5-13
pubmed:abstractText
Osteoblasts are controlled by the individual and combined effects of systemic and local growth regulators. Here we show functional and physical interactions between estradiol (17?E) and Wnt activated pathways in osteoblasts. 17?E increased gene promoter activity by the Wnt pathway transcriptional effector T cell factor (TCF) in an estrogen receptor (ER) dependent way. This occurred independently of its activity through traditional estrogen response elements and was not replicated by androgen receptor activation. 17?E also increased the stimulatory effect of LiCl on TCF activity, LiCl increased the stimulatory effect of 17?E through estrogen response elements, and both were further enhanced by a noncanonical Wnt receptor agonist (WAg) that functions independently of ?-catenin stabilization. In contrast to LiCl, WAg increased DNA synthesis and reduced relative collagen synthesis and alkaline phosphatase activity in otherwise untreated or 17?E stimulated cells. In addition, WAg suppressed Runx2, osterix, and alkaline phosphatase mRNA levels, and potently induced osteoprotegerin mRNA, whereas LiCl was ineffective alone and inhibitory in combination with 17?E. A definitive intersection between the 17?E and Wnt pathways occurred at the protein level, where ER? physically associated with TCF-4 independently of its ?-catenin binding domain. This interaction required ligand-dependent exposure of a TCF binding region that mapped to ER? domain E and was further enhanced by Wnt pathway activation. Our studies reveal highly focused co-regulatory effects between the 17?E and Wnt pathways in osteoblasts that involve activated ER? and TCF-4 and downstream changes in gene expression, osteoblast proliferation, and differentiated cell function.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
1879-0038
pubmed:author
pubmed:copyrightInfo
Copyright © 2011 Elsevier B.V. All rights reserved.
pubmed:issnType
Electronic
pubmed:day
15
pubmed:volume
479
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
16-28
pubmed:meshHeading
pubmed:year
2011
pubmed:articleTitle
?-Catenin independent cross-control between the estradiol and Wnt pathways in osteoblasts.
pubmed:affiliation
Yale University School of Medicine, Department of Surgery, New Haven, CT, 06520-8041, USA. thomas.mccarthy@yale.edu
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural