Roles for NF-kappaB and c-Fos in osteoclasts.
NF-kappaB 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-kappaB 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.
Boyce
Brendan F
BF
Department of Pathology and Laboratory Medicine, University of Rochester Medical Center, 601 Elmwood Avenue, Box 626, Rochester, NY 14642, USA. brendan_boyce@urmc.rochester.edu
Yamashita
Teruhito
T
Yao
Zhenqiang
Z
Zhang
Qian
Q
Li
Fang
F
Xing
Lianping
L
D000818:Animals; D001862:Bone Resorption / Q000378:metabolism; D002454:Cell Differentiation / Q000502:physiology*; D016207:Cytokines / Q000378:metabolism*; D004967:Estrogens / Q000172:deficiency; D006801:Humans; D016328:NF-kappa B / Q000378:metabolism*; D010000:Osteitis / Q000378:metabolism; D010010:Osteoclasts / Q000378:metabolism*; D015663:Osteoporosis, Postmenopausal / Q000378:metabolism; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism*
D016207:Cytokines; D004967:Estrogens; D016328:NF-kappa B; D016760:Proto-Oncogene Proteins c-fos