Paget's disease - A VDR coactivator disease?

Noriyoshi Kurihara, Seiichi Ishizuka, Anne Demulder, Cheikh Menaa, G. David Roodman

Research output: Contribution to journalArticle

17 Scopus citations

Abstract

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)2D 3 and form OCL at concentrations of 1,25-(OH)2D 3 that are physiologic rather than pharmacologic. The increased responsivity to 1,25-(OH)2D3 is not due to increased levels of the Vitamin D receptor (VDR) or to increased infinity of 1,25-(OH)2D3 for VDR. We have recently shown using GST-VDR chimeric protein pull-down assays that TAFII-17, a member of the TAFII-D transcription complex, is increased in OCL precursors from patients with Paget's disease compared to normals. We further showed that TAFII-17 can enhance VDR mediated gene transcription and allow formation of the transcription complex at very low levels of 1,25-(OH) 2D3. 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) 2D3 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.

Original languageEnglish (US)
Pages (from-to)321-325
Number of pages5
JournalJournal of Steroid Biochemistry and Molecular Biology
Volume89-90
DOIs
StatePublished - May 1 2004

Keywords

  • Coactivator
  • Osteoclasts
  • Paget's disease
  • Vitamin D receptor

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Endocrinology
  • Clinical Biochemistry
  • Cell Biology

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