Regulatory role of NF-κB in growth plate chondrogenesis and its functional interaction with Growth Hormone.

Nuclear Factor kappa B (NF-kB) is a family of transcription factors that participates in the regulation of cell proliferation, migration, and apoptosis. Impaired NF-kB activity appears to be involved in the pathophysiology of inflammatory states, autoimmune diseases, and cancer. Genetic manipulation in mice leading to impaired NF-kB function is associated with abnormal limb development and delayed bone growth. We have previously shown in rodent cultured chondrocytes and cultured metatarsal bones that NF-kB promotes longitudinal bone growth and growth plate chondrocyte function. These NF-kB growth-promoting effects appear to be facilitated by Growth Hormone (GH) and Insulin-like Growth factor-1 (IGF-1). These stimulatory effects of GH and IGF-1 on NF-kB activity are supported by observational evidence in humans; a number of individuals carrying mutations that alter NF-kB function exhibit growth failure and GH insensitivity.