Control of osteoclast activity and bone loss by IKK subunits: new targets for therapy.
Transcription factor NF-kappaB has been well recognized as a pivotal player in osteclastogenesis and inflammation-induced bone loss. Here, we discuss our 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
Maria Grazia
MG
Laboratory of Gene Regulation and Signal Transduction, School of Medicine, University of California, San Diego, 9500 Gilman Drive, La Jolla, California 92093, USA.
Karin
Michael
M
D000818:Animals; D017209:Apoptosis; D001172:Arthritis, Rheumatoid / Q000188:drug therapy / Q000378:metabolism*; D016723:Bone Remodeling; D001862:Bone Resorption; D051550:I-kappa B Kinase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism; D053245:RANK Ligand / Q000378:metabolism*; D053246:Receptor Activator of Nuclear Factor-kappa B / Q000378:metabolism*; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D016328:NF-kappa B; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; D047888:Receptors, Tumor Necrosis Factor, Type I; D014409:Tumor Necrosis Factor-alpha; D051550:I-kappa B Kinase