Roles for NF-κB and c-Fos in osteoclasts

NF-kappa B and c-Fos are transcription factors that are activated in immune cells and in most other cell types following stimulation by a variety of factors, including cytokines. growth factors. and hormones. They regulate the expression of a large number of genes, and both are activated in osteoclast precursors after RANKL, IL-1, or TNF bind to their respective receptors. However, of these cytokines. only RANKL is required for the induction of osteoclast formation in vivo. Nevertheless, it is likely that IL-1, TNF, and other cytokines participate in the upregulation of osteoclast formation seen in a variety of conditions that affect the skeleton in which cytokine production is increased, including estrogen deficiency and inflammatory bone diseases. In this review, the RANKL/ OPG/RANK system and roles for NF-kappa B and c-Fos in osteoclasts are reviewed along with our current understanding of how this system may be disrupted in common bone diseases, Such as postmenopausal osteoporosis, inflammatory arthritis. and Paget's disease.