Contributions of the measles virus nucleocapsid gene and the SQSTM1/p62P392L mutation to paget's disease

Noriyoshi Kurihara, 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


99 被引用数 (Scopus)


Paget's disease (PD) is characterized by abnormal osteoclasts (OCL) that secrete high IL-6 levels and induce exuberant bone formation. Because measles virus nucleocapsid gene (MVNP) and the p62P392L mutation are implicated in PD, marrows from 12 PD patients harboring p62P392L 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 p62P394L 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 p62P394L developed dramatic Paget's-like bone lesions. These results suggest that p62 P394L and IL-6 induction by MVNP play key roles in PD.

ジャーナルCell Metabolism
出版ステータスPublished - 1月 5 2011

ASJC Scopus subject areas

  • 生理学
  • 分子生物学
  • 細胞生物学


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