title: Control of osteoclast activity and bone loss by IKK subunits: new targets for therapy.
abstract: 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.
authors.affiliation: Laboratory of Gene Regulation and Signal Transduction, School of Medicine, University of California, San Diego, 9500 Gilman Drive, La Jolla, California 92093, USA.
authors.forename: Maria Grazia
authors.initials: MG
authors.lastname: Ruocco
authors.forename: Michael
authors.initials: M
authors.lastname: Karin
mesh_terms: 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
chemical_list: 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