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.
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Novack, D., Yang, C., Davis, J., McCoy, K. (2013). NF-κB and Inflammatory Bone Loss: “Alternative” Family Members Take Their Place at the Table. In: Choi, Y. (eds) Osteoimmunology. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-5366-6_2
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DOI: https://doi.org/10.1007/978-1-4614-5366-6_2
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