Endocrinol Metab.  2015 Mar;30(1):35-44. 10.3803/EnM.2015.30.1.35.

NF-kappaB-Mediated Regulation of Osteoclastogenesis

Affiliations
  • 1Department of Pathology and Laboratory Medicine, University of Rochester Medical Center, Rochester, NY, USA. Brendan_Boyce@urmc.rochester.edu

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-kappa B (NF-kappaB) signaling and that this is activated in response to the essential osteoclastogenic cytokine, receptor activator of NF-kappaB 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-kappaB 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-kappaB signaling that can limit osteoclast formation through the NF-kappaB 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-kappaB signaling is involved in the positive and negative regulation of cytokine-mediated osteoclast formation and activation.

Keyword

NF-kappa B; Osteoclasts; RANK ligand; Tumor necrosis factor; TNF receptor-associated factor 3; NF-kappa B kinase

MeSH Terms

Cytokines
NF-kappa B
NFATC Transcription Factors
Osteoclasts
RANK Ligand
Receptor Activator of Nuclear Factor-kappa B
TNF Receptor-Associated Factor 3
Tumor Necrosis Factor-alpha
Cytokines
NF-kappa B
NFATC Transcription Factors
RANK Ligand
Receptor Activator of Nuclear Factor-kappa B
TNF Receptor-Associated Factor 3
Tumor Necrosis Factor-alpha
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