NF-κB is a critical signal for osteoclast (OC) differentiation downstream of RANKL, and its disruption blocks bone loss in a variety of disease models in mice. Differently from other TNF family members, RANKL activates both the classical NF-κB pathway, activating p65 and cRel, and the alternative pathway, inducing expression and activation of RelB. Our studies on the role of individual NF-κB subunits have demonstrated that p65 is important for OC precursor survival during a critical period of differentiation but is not necessary for transcription of the OC differentiation program [1]. In contrast, RelB is required for OC differentiation in vitro and for pathological bone loss in vivo [2]. Both deletion and activation of NIK, the upstream kinase regulating RelB activation, significantly modulates osteoclastogenesis, especially in models of inflammatory arthritis. Thus, the alternative NF-κB pathway represents an interesting potential target for the control of bone loss in diseases such as rheumatoid arthritis.

Original languageEnglish
Title of host publicationOsteoimmunology
Subtitle of host publicationInteractions of the immune and skeletal systems
PublisherSpringer New York
Number of pages4
ISBN (Electronic)9781461453666
ISBN (Print)1461453658, 9781461453659
StatePublished - Oct 1 2013


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