Insights into the pathogenesis of Paget's disease

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

31 Citations (Scopus)

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 publicationAnnals of the New York Academy of Sciences
Pages176-180
Number of pages5
Volume1192
DOIs
StatePublished - Mar 2010
Externally publishedYes

Publication series

NameAnnals of the New York Academy of Sciences
Volume1192
ISSN (Print)00778923
ISSN (Electronic)17496632

Fingerprint

Nucleocapsid
Measles virus
Bone
Viruses
Osteoclasts
Mutation
Genes
Bone Remodeling
Bone Resorption
Osteogenesis
Gene expression
Transgenic Mice
Bone Marrow
Gene Expression
Bone and Bones
Infection

Keywords

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

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

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

Insights into the pathogenesis of Paget's disease. / Roodman, G. David.

Annals of the New York Academy of Sciences. Vol. 1192 2010. p. 176-180 (Annals of the New York Academy of Sciences; Vol. 1192).

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

Roodman, GD 2010, Insights into the pathogenesis of Paget's disease. in Annals of the New York Academy of Sciences. vol. 1192, Annals of the New York Academy of Sciences, vol. 1192, pp. 176-180. https://doi.org/10.1111/j.1749-6632.2009.05214.x
Roodman GD. Insights into the pathogenesis of Paget's disease. In Annals of the New York Academy of Sciences. Vol. 1192. 2010. p. 176-180. (Annals of the New York Academy of Sciences). https://doi.org/10.1111/j.1749-6632.2009.05214.x
Roodman, G. David. / Insights into the pathogenesis of Paget's disease. Annals of the New York Academy of Sciences. Vol. 1192 2010. pp. 176-180 (Annals of the New York Academy of Sciences).
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