Role of TAFII-17, a VDR binding protein, in the increased osteoclast formation in Paget's disease

Noriyoshi Kurihara, Sakamuri V. Reddy, Norie Araki, Seiichi Ishizuka, Keiichi Ozono, Jillian Cornish, Tim Cundy, Frederick R. Singer, G. David Roodman

Research output: Contribution to journalArticle

44 Scopus citations

Abstract

In contrast to normal OCL precursors, pagetic OCL precursors express MVNP and form OCL at physiologic concentrations of 1,25(OH)2D3, as do normal OCL precursors transfected with the MVNP gene. Using a GST-VDR chimeric protein, we identified TAFII-17 as VDR binding protein expressed by pagetic OCL precursors and MVNP transduced normal OCL precursors. TAFII-17 was in part responsible for the increased 1,25(OH) 2D3 responsivity of pagetic OCL precursors. Introduction: Pagetic osteoclasts (OCLs) and their precursors express measles virus nucleocapsid protein (MVNP) and form large numbers of OCLs at low concentrations of 1,25-dihydroxyvitamin D3 [1,25(OH)2D3]. Similarly, normal OCL precursors transfected with MVNP also form OCLs at low concentrations of 1,25(OH)2D3. These results suggest that expression of MVNP in OCL precursors enhances vitamin D receptor (VDR)-mediated gene transcription. Materials and Methods: To determine the mechanism for the increased OCL formation capacity of pagetic OCL precursors in response to 1,25(OH)2D3, lysates from pagetic and MVNP-transduced normal OCL precursors were incubated with a GST-VDR chimeric protein. Results: A 17-kDa peptide that bound VDR was detected in MVNP-transduced cells and pagetic OCL precursors treated with 1,25(OH)2D3. This peptide was identified as TAFII-17, a component of the TFIID transcription complex. Expression of increased levels of TAFII-17 in cells allowed TAFII-17 to bind to VDR at low concentrations of 1,25(OH) 2D3. An antisense oligonucelotide (AS-ODN) to TAF II-17 significantly decreased OCL formation in response to 1,25(OH)2D3 in pagetic but not normal marrow cultures by ∼40%. Transfection of TAFII-17 or MVNP into NIH3T3 cells increased VDR transcriptional activity as measured by DR-3 reporter assays. Conclusion: These data show that expression of the MVNP gene in OCL precursors results in increased levels of TAFII-17. TAFII-17 can bind VDR at low concentrations of 1,25(OH)2D3. These results suggest that MVNP expression in Paget's OCL precursors increases expression of a component(s) of the VDR transcription complex that can increase OCL formation.

Original languageEnglish (US)
Pages (from-to)1154-1164
Number of pages11
JournalJournal of Bone and Mineral Research
Volume19
Issue number7
DOIs
StatePublished - Jul 1 2004
Externally publishedYes

Keywords

  • 1,25-dihydroxyvitamin D
  • Bone marrow cultures
  • Osteoclast formation
  • Paget's disease
  • TAF-17

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Orthopedics and Sports Medicine

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