Functions of nuclear factor kappaB in bone.

Nuclear factor kappaB (NF-kappaB) is a set of multifunctional transcription factors that regulate expression of genes involved in numerous normal cellular activities. They also are activated in many inflammatory and neoplastic conditions in which their expression may be stimulated by proinflammatory cytokines. NF-kappaB, in turn, regulates the expression of cytokines and so can mediate autocrine self-amplifying cycles of cytokine release and NF-kappaB activation, leading to maintenance of inflammatory reactions beyond the initial stimulus, as seen in rheumatoid arthritis and asthma. Since discovery of the requirement of NF-kappaB for basal and cytokine-induced osteoclast formation in the mid-1990s, much has been learned about the role of NF-kappaB in bone. NF-kappaB has roles in skeletal development, endochondral ossification, osteoclast and osteoblast functions, and common bone diseases. NF-kappaB inhibitors have been developed, but none have made it to clinical trials for the treatment of common bone diseases. Here we review the roles for NF-kappaB in bone and in common bone diseases.