ESPE Abstracts (2015) 84 WG1.2

The Role of NFkB in Growth Plate Chondrogenesis

Francesco De Luca

St. Christopher’s Hospital for Children, Philadelphia, Pennsylvania, USA

Nuclear Factor kappa B (NF-κB) is a group of seven transcription factors, including p65 (RelA), c-Rel, RelB, p50/p105 (NF-κB1), and p52/p100 (NF-κB2). Upon activation by a wide variety of stimuli, NF-κB translocates to the nucleus, where it modulates the expression of target genes involved in cell growth, survival, and death.

Previous evidence indicates that NF-κB regulates bone growth and development. Mice deficient in both the NF-κB subunits p50 and p52 have retarded growth and shortened long bones. In addition, we have previously shown that the NF-κB subunit 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.

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