Abstract
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 language | English |
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Title of host publication | Osteoimmunology |
Subtitle of host publication | Interactions of the immune and skeletal systems |
Publisher | Springer New York |
Pages | 3-6 |
Number of pages | 4 |
ISBN (Electronic) | 9781461453666 |
ISBN (Print) | 1461453658, 9781461453659 |
DOIs | |
State | Published - Oct 1 2013 |