IKK{beta} as a target for treatment of inflammation induced bone loss.
The transcription factor nuclear factor (NF)-kappaB is well recognised as a pivotal player in osteoclastogenesis and inflammation induced bone loss. Here, the authors discuss their recent results, obtained using a genetic approach in mice, that indicate the importance of IKKbeta, and not IKKalpha, as a transducer of signals from receptor activator of NF-kappaB (RANK) to NF-kappaB. Ablation of IKKbeta results in lack of osteoclastogenesis and unresponsiveness of IKKbeta deficient mice to inflammation induced bone loss. In the need of a more effective therapy for the treatment of inflammatory diseases causing bone resorption, specific inhibition of IKKbeta represents a logical alternative strategy to the current therapies.
Ruocco
M G
MG
Laboratory of Gene Regulation and Signal Transduction, School of Medicine, University of California at San Diego, La Jolla, CA, USA.
Karin
M
M
D000818:Animals; D001862:Bone Resorption / Q000188:drug therapy / Q000201:enzymology / Q000209:etiology*; D006023:Glycoproteins / Q000502:physiology; D006801:Humans; D051550:I-kappa B Kinase / Q000037:antagonists & inhibitors / Q000502:physiology*; D007249:Inflammation / Q000150:complications*; D051379:Mice; D053244:Osteoprotegerin; D018160:Receptors, Cytoplasmic and Nuclear / Q000502:physiology; D018124:Receptors, Tumor Necrosis Factor / Q000502:physiology; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology
D006023:Glycoproteins; D053244:Osteoprotegerin; D018160:Receptors, Cytoplasmic and Nuclear; D018124:Receptors, Tumor Necrosis Factor; C506030:TNFRSF11B protein, human; C506031:Tnfrsf11b protein, mouse; D014409:Tumor Necrosis Factor-alpha; D051550:I-kappa B Kinase