title: NF-κB-Mediated Regulation of Osteoclastogenesis.
abstract: Osteoclasts are multinucleated cells formed mainly on bone surfaces in response to cytokines by fusion of bone marrow-derived myeloid lineage precursors that circulate in the blood. Major advances in understanding of the molecular mechanisms regulating osteoclast formation and functions have been made in the past 20 years since the discovery that their formation requires nuclear factor-κB (NF-κB) signaling and that this is activated in response to the essential osteoclastogenic cytokine, receptor activator of NF-κB ligand (RANKL), which also controls osteoclast activation to resorb (degrade) bone. These studies have revealed that RANKL and some pro-inflammatory cytokines, including tumor necrosis factor, activate NF-κB and downstream signaling, including c-Fos and nuclear factor of activated T-cells, cytoplasmic 1 (NFATc1), and inhibition of repressors of NFATc1 signaling, to positively regulate osteoclast formation and functions. However, these cytokines also activate NF-κB signaling that can limit osteoclast formation through the NF-κB signaling proteins, TRAF3 and p100, and the suppressors of c-Fos/NFATc1 signaling, IRF8, and RBP-J. This paper reviews current understanding of how NF-κB signaling is involved in the positive and negative regulation of cytokine-mediated osteoclast formation and activation.
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Rochester Medical Center, Rochester, NY, USA. Brendan_Boyce@urmc.rochester.edu.
authors.forename: Brendan F
authors.initials: BF
authors.lastname: Boyce
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Rochester Medical Center, Rochester, NY, USA.
authors.forename: Yan
authors.initials: Y
authors.lastname: Xiu
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Rochester Medical Center, Rochester, NY, USA.
authors.forename: Jinbo
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Rochester Medical Center, Rochester, NY, USA.
authors.forename: Lianping
authors.initials: L
authors.lastname: Xing
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Rochester Medical Center, Rochester, NY, USA.
authors.forename: Zhenqiang
authors.initials: Z
authors.lastname: Yao
keywords: NF-κB; NF-κB kinase; Osteoclasts; RANK ligand; TNF receptor-associated factor 3; Tumor necrosis factor
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