Vitamin D and Paget's Disease

Research output: Chapter in Book/Report/Conference proceedingChapter

Abstract

Paget's disease (PD) is characterized by increased focal bone resorption accompanied by exuberant bone formation; with the primary abnormality in osteoclasts (OCLs). Viral and genetic etiologies have been implicated in PD. OCL precursors (OCL-pre) from 70% of PD patients express measles virus nucleocapsid protein gene (MVNP), and 30% of PD patients harbor a mutated gene linked to PD; the most frequent is the p62P392L mutation in sequestosome 1. MVNP in OCL-pre induces high levels of TAF12, a vitamin D nuclear receptor (VDR) coactivator that enhances VDR-mediated transcription and VDR half-life in the presence of 1,25(OH)D3. This allows OCL formation at physiologic rather than pharmacologic levels of 1,25(OH)D3. In contrast, PD patients harboring p62P392L but whose OCL-pre lack MVNP, only form OCLs at pharmacologic 1,25(OH)D3 levels. However, marrow stromal cells harboring p62P392L express high TAF12 levels and produce increased amounts of RANKL when treated with physiologic levels of 1,25(OH)D3, supporting a major role for 1,25(OH)D3 in PD.

Original languageEnglish (US)
Title of host publicationHealth, Disease and Therapeutics
PublisherElsevier Inc.
Pages571-579
Number of pages9
Volume2
ISBN (Electronic)9780128099650
ISBN (Print)9780128099643
DOIs
StatePublished - Dec 14 2017

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Keywords

  • Coactivators
  • Osteoclasts
  • Paget's disease
  • TAF12
  • VDR responsivity

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Kurihara, N., & Roodman, G. D. (2017). Vitamin D and Paget's Disease. In Health, Disease and Therapeutics (Vol. 2, pp. 571-579). Elsevier Inc.. https://doi.org/10.1016/B978-0-12-809963-6.00085-7