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Insights into the pathogenesis of Paget's disease
Author(s) -
Roodman G. David
Publication year - 2010
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1111/j.1749-6632.2009.05214.x
Subject(s) - pathogenesis , sequestosome 1 , paget's disease of bone , measles virus , bone resorption , mutation , disease , bone remodeling , bone marrow , pathology , medicine , immunology , cancer research , biology , gene , genetics , measles , antibody , vaccination , immunoglobulin light chain
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 p62 P392L 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 p62 P392L 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.