Jawing about TNF: new hope for cherubism.
Mutations in the SH3-domain binding protein 2 (SH3BP2) are known to cause a rare childhood disorder called cherubism that is characterized by inflammation and bone loss in the jaw, but the mechanism has remained unclear. In this issue, Ueki et al. (Ueki et al., 2007) now demonstrate that a cherubism mutation activates mouse Sh3bp2 resulting in enhanced production of the cytokine TNF-alpha by myeloid cells, leading to both bone loss and inflammation.
Novack
Deborah Veis
DV
Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA. novack@wustl.edu
Faccio
Roberta
R
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001862:Bone Resorption / Q000473:pathology; D002454:Cell Differentiation / Q000187:drug effects; D002636:Cherubism / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D004195:Disease Models, Animal; D007249:Inflammation / Q000378:metabolism; D016173:Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D051379:Mice; D009154:Mutation / Q000235:genetics; D010010:Osteoclasts / Q000166:cytology / Q000187:drug effects / Q000473:pathology; D053245:RANK Ligand / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
D048868:Adaptor Proteins, Signal Transducing; D053245:RANK Ligand; C484644:Sh3bp2 protein, mouse; D014409:Tumor Necrosis Factor-alpha; D016173:Macrophage Colony-Stimulating Factor