Vol 21: Pathobiology of Pagets Disease of Bone.Report as inadecuate



 Vol 21: Pathobiology of Pagets Disease of Bone.


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This article is from Journal of Bone Metabolism, volume 21.AbstractPagets disease of bone is characterized by highly localized areas of increased bone resorption accompanied by exuberant, but aberrant new bone formation with the primary cellular abnormality in osteoclasts. Pagets disease provides an important paradigm for understanding the molecular mechanisms regulating both osteoclast formation and osteoclast-induced osteoblast activity. Both genetic and environmental etiologies have been implicated in Pagets disease, but their relative contributions are just beginning to be defined. To date, the only gene with mutations in the coding region linked to Pagets disease is sequestosome-1 SQSTM1, which encodes the p62 protein, and these mutations lead to elevated cytokine activation of NF-B in osteoclasts but do not induce a -pagetic osteoclast- phenotype. Further, genetic mutations linked to Pagets appear insufficient to cause Pagets disease and additional susceptibility loci or environmental factors may be required. Among the environmental factors suggested to induce Pagets disease, chronic measles MV infection has been the most studied. Expression of the measles virus nucleocapsid gene MVNP in osteoclasts induces pagetic-like osteoclasts and bone lesions in mice. Further, mice expressing both MVNP in osteoclasts and germline mutant p62 develop dramatic pagetic bone lesions that were strikingly similar to those seen in patients with Pagets disease. Thus, interactions between environmental and genetic factors appear important to the development of Pagets disease. In this article we review the mechanisms responsible for the effects of mutant p62 gene expression and MVNP on osteoclast and osteoblast activity, and how they may contribute to the development of Pagets disease of bone.



Author: Galson, Deborah L.; Roodman, G. David

Source: https://archive.org/







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