Etanercept administration to neonatal SH3BP2 knock-in cherubism mice prevents TNF-α-induced inflammation and bone loss.

ABSTRACT: Cherubism is a genetic disorder of the craniofacial skeleton caused by gain-of-function mutations in the signaling adaptor protein, SH3-domain binding protein 2 (SH3BP2). In a knock-in mouse model for cherubism, we previously demonstrated that homozygous mutant mice develop T/B cell-independent systemic macrophage inflammation leading to bone erosion and joint destruction. Homozygous mice develop multiostotic bone lesions whereas cherubism lesions in humans are limited to jawbones. We identified a critical role of tumor necrosis factor α (TNF-α) in the development of autoinflammation by creating homozygous TNF-α-deficient cherubism mutants, in which systemic inflammation and bone destruction were rescued. In this study, we examined whether postnatal administration of an anti-TNF-α antagoni

SUBMITTER: Yoshitaka T 

PROVIDER: S-EPMC4131552 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature