Document Detail


Paget's disease-a VDR coactivator disease?
MedLine Citation:
PMID:  15225793     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Paget's disease is the most exaggerated example of bone remodeling with increased osteoclastic bone resorption followed by excessive bone formation. One of the earliest findings in our studies of Paget's disease is that pagetic osteoclast (OCL) precursors are hyper-responsive to 1,25-(OH)(2)D(3) and form OCL at concentrations of 1,25-(OH)(2)D(3) that are physiologic rather than pharmacologic. The increased responsivity to 1,25-(OH)(2)D(3) is not due to increased levels of the Vitamin D receptor (VDR) or to increased infinity of 1,25-(OH)(2)D(3) for VDR. We have recently shown using GST-VDR chimeric protein pull-down assays that TAF(II)-17, a member of the TAF(II)-D transcription complex, is increased in OCL precursors from patients with Paget's disease compared to normals. We further showed that TAF(II)-17 can enhance VDR mediated gene transcription and allow formation of the transcription complex at very low levels of 1,25-(OH)(2)D(3). In addition, coactivators of VDR including CPB300 and DRIP205 are also increased in OCL precursors from Paget's patients. These data suggest that the enhanced sensitivity of OCL precursors for 1,25-(OH)(2)D(3) in Paget's disease results from increased expression of coactivators of VDR and suggest that part of the pathophysiology underlying OCL formation in Paget's disease may result from enhanced expression of VDR coactivators.
Authors:
Noriyoshi Kurihara; Seiichi Ishizuka; Anne Demulder; Cheikh Menaa; G David Roodman
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Publication Detail:
Type:  Journal Article; Review    
Journal Detail:
Title:  The Journal of steroid biochemistry and molecular biology     Volume:  89-90     ISSN:  0960-0760     ISO Abbreviation:  J. Steroid Biochem. Mol. Biol.     Publication Date:  2004 May 
Date Detail:
Created Date:  2004-06-30     Completed Date:  2004-08-31     Revised Date:  2005-11-16    
Medline Journal Info:
Nlm Unique ID:  9015483     Medline TA:  J Steroid Biochem Mol Biol     Country:  England    
Other Details:
Languages:  eng     Pagination:  321-5     Citation Subset:  IM    
Affiliation:
Department of Medicine/Hematology, University of Pittsburgh, Kaufmann Medical Building, Suite 601, 3471 Fifth Avenue, Pittsburgh, PA 15213, USA.
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MeSH Terms
Descriptor/Qualifier:
Calcitriol / blood,  physiology
Humans
Osteitis Deformans / physiopathology*
Receptors, Calcitriol / physiology*
Recombinant Fusion Proteins / metabolism
Transcription, Genetic / physiology
Chemical
Reg. No./Substance:
0/Receptors, Calcitriol; 0/Recombinant Fusion Proteins; 32222-06-3/Calcitriol

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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