NF-kappaB2 (p100) limits TNF-alpha-induced osteoclastogenesis.
Bone undergoes a continuous cycle of renewal, and osteoclasts--the cells responsible for bone resorption--play a pivotal role in bone homeostasis. This resorption is largely mediated by inflammatory cytokines such as TNF-alpha. In this issue of the JCI, Yao et al. demonstrate that the NF-kappaB precursor protein NF-kappaB2 (p100) acts as a negative regulator of osteoclastogenesis (see the related article beginning on page 3024). TNF-alpha induced a sustained accumulation of p100 in osteoclast precursors, and TNF-alpha-induced osteoclast formation was markedly increased in Nfkb2-/- mice. They also found that TNF receptor-associated factor 3 (TRAF3) is involved in the posttranslational regulation of p100 expression. These results suggest that blockade of the processing of p100 is a novel strategy to treat TNF-alpha-related bone diseases such as RA.
Tanaka
Sakae
S
Department of Orthopaedic Surgery, Faculty of Medicine, University of Tokyo, Bunkyo-ku, Tokyo, Japan. tanakas-ort@h.u-tokyo.ac.jp
Nakano
Hiroyasu
H
D000818:Animals; D002454:Cell Differentiation / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D052003:NF-kappa B p52 Subunit / Q000235:genetics / Q000378:metabolism*; D010010:Osteoclasts / Q000166:cytology / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology; D048008:TNF Receptor-Associated Factor 3 / Q000235:genetics / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
D052003:NF-kappa B p52 Subunit; D048008:TNF Receptor-Associated Factor 3; D014409:Tumor Necrosis Factor-alpha