Etiologic factors in Paget's disease of bone.
Paget's disease of bone is a chronic focal skeletal disorder characterized by increased bone resorption by the osteoclasts. Paramyxoviral gene products have been detected in pagetic osteoclasts. Paget's disease is an autosomal dominant trait with genetic heterogeneity. Several mutations in the ubiquitin-associated (UBA) domain of sequestosome 1 (SQSTM1/p62) have been identified in patients with Paget's disease. Similarly, mutations in the valosin-containing protein (VCP) gene have been shown to cause inclusion body myopathy associated with Paget's disease of bone and frontotemporal dementia. In addition, gene polymorphisms and enhanced levels of cytokine/growth factors associated with Paget's disease have been identified. However, the etiologic factors in Paget's disease remain elusive. A cause and effect relationship for the paramyxoviral infection and SQSTM1/ p62 gene mutations responsible for pagetic osteoclast development and disease severity are unclear. This article will highlight the etiologic factors involved in the pathogenesis of Paget's disease.
Reddy
S V
SV
Children's Research Institute, Medical University of South Carolina, 173 Ashley Avenue, Charleston, South Carolina 29425, USA. reddysv@musc.edu
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D001862:Bone Resorption; D008040:Genetic Linkage; D006801:Humans; D009154:Mutation; D010001:Osteitis Deformans / Q000209:etiology* / Q000235:genetics / Q000821:virology; D010010:Osteoclasts / Q000473:pathology; D018184:Paramyxoviridae Infections / Q000150:complications; D011110:Polymorphism, Genetic; D011506:Proteins / Q000235:genetics; D000071456:Sequestosome-1 Protein
D048868:Adaptor Proteins, Signal Transducing; D011506:Proteins; C099718:SQSTM1 protein, human; D000071456:Sequestosome-1 Protein