期刊
BONE
卷 43, 期 5, 页码 819-825出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.bone.2008.06.015
关键词
Paget's disease; Genetic; Osteoclast; Osteoblast; RANK
Paget's disease of bone is a common condition characterised by increased and disorganised bone turnover which can affect one or several bones throughout the skeleton. These abnormalities disrupt normal bone architecture and lead to various complications Such as bone pain osteoarthritis, pathological fracture, bone deformity, deafness, and nerve compression syndromes. Genetic factors play an important role in PDB and mutations or polymorphisms have been identified ill four genes that cause classical Paget's disease and related syndromes. These include TNFRSF11A, which encodes RANK, TNFRSF11B which encodes osteoprotegerin, VCP which encodes p97, and SQSTM1 which encodes p62. All of these genes play a role in the RANK-NF kappa B signalling pathway and it is likely that the mutations predispose to PDB by disrupting normal signalling, leading to osteoclast activation. Although Paget's has traditionally be considered a disease of the osteoclast there is evidence that stromal cell function and osteoblast function are also abnormal which, might account for the fact that the disease is associated with increased bone formation as well as resorption. Environmental factors also Contribute to Paget's disease. Most research has focused on paramyxovirus infection as a possible environmental trigger but evidence in favour of the involvement of viruses in the disease remains conflicting. Other factors which have been implicated as possible disease triggers include mechanical loading, dietary Calcium and environmental toxins. Further work will be required to identify additional genetic variants that predispose to Paget's disease and to determine how the causal mutations and predisposing polymorphisms interact with environmental factors to influence bone cell function and cause the focal bone lesions that are characteristic of the disease. (c) 2008 Elsevier Inc. All rights reserved.
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