Role of Nuclear Factor Kappa B (NF-κB) in Growth Plate Chondrogenesis.

Abstract Nuclear Factor kappa B (NF-κB) is a group of seven transcription factors. Upon activation by a variety of stimuli, NF-κB translocates to the nucleus and modulates the expression of target genes involved in cell growth, survival, and death. Previous evidence indicates that NF-κB regulates bone growth and development. We have shown that the NF-κB p65 is expressed in the growth plate and facilitates longitudinal bone growth by inducing chondrocyte proliferation and differentiation and by preventing apoptosis. Furthermore, we have demonstrated in rodents that NF-κB expressed in growth plate chondrocytes mediates the promoting effects of GH and IGF-1 on longitudinal bone growth and growth plate chondrogenesis. Lastly, functional studies carried out in two children with growth failure and GH insensitivity, and affected by two different mutations impairing NF-κB activation, indicate that NF-κB also mediates the growth-promoting effects of GH in humans.