Insights into the pathogenesis of Paget's disease

Research output: Chapter in Book/Report/Conference proceedingConference contribution

32 Scopus citations

Abstract

Paget's disease (PD) affects approximately 1.5 million persons in the United States and is characterized by grossly distorted bone remodeling, with increases in bone resorption and formation. Both environmental and genetic factors may contribute to the pathogenesis of PD. Mutations in sequestosome-1 (p62) occur in 25-30% of patients with familial PD, and in ∼10% of patients with sporadic PD. Preclinical studies suggest that the p62P392L mutation predisposes patients to developing PD rather than causing it. Other studies have suggested that PD results from a chronic paramyxoviral infection. Transgenic mice expressing the measles virus nucleocapsid gene (MVNP) in osteoclasts (OCLs) develop pagetic bone lesions. Further, approximately 70% of patients harboring the p62P392L mutation we studied have detectable MVNP transcripts, and inhibiting MVNP expression in bone marrow cultures from those patients blocked pagetic OCL formation. These studies suggest that both genetic and environmental factors contribute to PD.

Original languageEnglish (US)
Title of host publicationSkeletal Biology and Medicine
PublisherBlackwell Publishing Inc.
Pages176-180
Number of pages5
ISBN (Print)9781573317856
DOIs
StatePublished - Mar 2010

Publication series

NameAnnals of the New York Academy of Sciences
Volume1192
ISSN (Print)0077-8923
ISSN (Electronic)1749-6632

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Keywords

  • Measles virus
  • Paget's disease
  • Sequestosome-1

ASJC Scopus subject areas

  • Neuroscience(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • History and Philosophy of Science

Cite this

Roodman, G. D. (2010). Insights into the pathogenesis of Paget's disease. In Skeletal Biology and Medicine (pp. 176-180). (Annals of the New York Academy of Sciences; Vol. 1192). Blackwell Publishing Inc.. https://doi.org/10.1111/j.1749-6632.2009.05214.x