Abstract
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.