IκB kinase (IKK)β, but not IKKα, is a critical mediator of osteoclast survival and is required for inflammation-induced bone loss

Transcription factor, nuclear factor kappa B (NF-kappa B), is required for osteoclast formation in vivo and mice lacking both of the NF-kappa B p50 and p52 proteins are osteopetrotic. Here we address the relative roles of the two catalytic subunits of the I kappa B kinase (IKK) complex that mediate NF-kappa B activation, IKK alpha and IKK beta, in osteoclast formation and inflammation-induced bone loss. Our findings point out the importance of the IKK beta subunit as a transducer of signals from receptor activator of NF-kappa B ( RANK) to NF-kappa B. Although IKK alpha is required for RANK ligand-induced osteoclast formation in vitro, it is not needed in vivo. However, IKK beta is required for osteoclastogenesis in vitro and in vivo. IKK beta also protects osteoclasts and their progenitors from tumor necrosis factor alpha-induced apoptosis, and its loss in hematopoietic cells prevents inflammation-induced bone loss.