Role of NF-κB in the skeleton

Since the discovery that deletion of the NF-kappa B subunits p50 and p52 causes osteopetrosis in mice, there has been considerable interest in the role of NF-kappa B signaling in bone. NF-kappa B controls the differentiation or activity of the major skeletal cell types - osteoclasts, osteoblasts, osteocytes and chondrocytes. However, with five NF-kappa B subunits and two distinct activation pathways, not all NF-kappa B signals lead to the same physiologic responses. In this review, we will describe the roles of various NF-kappa B proteins in basal bone homeostasis and disease states, and explore how NF-kappa B inhibition might be utilized therapeutically.