期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2014
卷号：111
期号：3
页码：1066-1071
DOI：10.1073/pnas.1318688111
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：The immune system plays an important role in the pathophysiology of many acute and chronic bone disorders, but the specific inflammatory networks that regulate individual bone disorders remain to be elucidated. Here, we characterized the osteoimmunological underpinnings of osteolytic bone disease in Pstpip2cmo mice. These mice carry a homozygous L98P missense mutation in the Pombe Cdc15 homology family phosphatase PSTPIP2 that is responsible for the development of a persistent autoinflammatory disease resembling chronic recurrent multifocal osteomyelitis in humans. We found that improper regulation of IL-1{beta} production resulted in secondary induction of inflammatory cytokines, inflammatory cell infiltration in the bone, and unremitting bone inflammation. Aberrant Il1{beta} expression precedes the development of osteolytic damage in young Pstpip2cmo mice, and genetic deletion of Il1r and Il1{beta
