| Literature DB >> 21195346 |
Noriyoshi Kurihara1, Yuko Hiruma, Kei Yamana, Laëtitia Michou, Côme Rousseau, Jean Morissette, Deborah L Galson, Jumpei Teramachi, Hua Zhou, David W Dempster, Jolene J Windle, Jacques P Brown, G David Roodman.
Abstract
Paget's disease (PD) is characterized by abnormal osteoclasts (OCL) that secrete high <span class="Gene">IL-6 levels and induce exuberant bone formation. Because measles virus nucleocapsid gene (MVNP) and the p62(P392L) mutation are implicated in PD, marrows from 12 PD patients harboring p62(P392L) and eight normals were tested for MVNP expression and pagetic OCL formation. Eight out of twelve patients expressed MVNP and formed pagetic OCL in vitro, which were inhibited by antisense-MVNP. Four out of twelve patients lacked MVNP and formed normal OCL that were hyperresponsive to RANKL but unaffected by antisense-MVNP. Similarly, mice expressing only p62(P394L) formed normal OCL, while mice expressing MVNP in OCL, with or without p62(P394L), developed pagetic OCL and expressed high IL-6 levels dependent on p38MAPK activation. IL-6 deficiency in MVNP mice abrogated pagetic OCL development in vitro. Mice coexpressing MVNP and p62(P394L) developed dramatic Paget's-like bone lesions. These results suggest that p62(P394L) and IL-6 induction by MVNP play key roles in PD. Copyright ÂEntities:
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Year: 2011 PMID： 21195346 PMCID： PMC3025409 DOI： 10.1016/j.cmet.2010.12.002
Source DB: PubMed Journal: Cell Metab ISSN： 1550-4131 Impact factor: 27.287