NF-κB2 (p100) 限制 TNF-α 诱导的破骨细胞生成。
NF-kappaB2 (p100) limits TNF-alpha-induced osteoclastogenesis.
机构信息
Department of Orthopaedic Surgery, Faculty of Medicine, University of Tokyo, Bunkyo-ku, Tokyo, Japan.
出版信息
J Clin Invest. 2009 Oct;119(10):2879-81. doi: 10.1172/JCI40629. Epub 2009 Sep 21.
Abstract
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.
摘要
骨骼经历着持续不断的更新循环，破骨细胞——负责骨吸收的细胞——在骨稳态中起着关键作用。这种吸收在很大程度上是由炎症细胞因子如 TNF-α介导的。在本期 JCI 中，Yao 等人表明，NF-κB 前体蛋白 NF-κB2（p100）作为破骨细胞生成的负调节剂（见第 3024 页开始的相关文章）。TNF-α诱导破骨细胞前体中 p100 的持续积累，并且 Nfkb2-/- 小鼠中 TNF-α诱导的破骨细胞形成显著增加。他们还发现 TNF 受体相关因子 3（TRAF3）参与 p100 表达的翻译后调节。这些结果表明，阻断 p100 的加工是治疗 TNF-α 相关骨病如 RA 的一种新策略。
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