Xing Lianping, Carlson Louise, Story Beryl, Tai Zhenxing, Keng Peter, Siebenlist Ulrich, Boyce Brendan F
Department of Pathology and Laboratory Medicine, University of Rochester Medical Center, Rochester, New York 14642, USA.
J Bone Miner Res. 2003 Feb;18(2):260-9. doi: 10.1359/jbmr.2003.18.2.260.
Interleukin (IL)-1 is implicated in postmenopausal- and inflammation-mediated bone loss. Its expression is regulated by NF-kappaB and vice versa. To examine the role of NF-kappaB p50 and p52 (they are required for osteoclast formation during embryonic development) in IL-1-induced resorption, we used various NF-kappaB knockout (KO) mice, including p50-/- and p52-/- single KO, p50-/- and p52+/- (3/4KO), and p50-/- and p52-/- double KO (dKO) mice. IL-1 increased blood calcium and bone resorption in wild-type (wt), p50, and p52 single KO mice, but not in 3/4KO or dKO mice. Osteoclast formation was impaired in bone marrow cultures from 3/4KO compared with single KO and wt mice treated with IL-1. IL-1 receptor expression was similar in colony forming unit-granulocyte macrophage (CFU-GM) colony cells from wt and dKO mice. However, IL-1 promoted CFU-GM colony formation and survival as well as the formation, activity, and survival of osteoclasts generated from these colonies from wt mouse splenocytes, but not from dKO splenocytes. No difference in expression of the osteoclast regulatory cytokines, RANKL, and OPG, was observed in osteoblasts from wt and dKO mice. Thus, expression of either NF-kappaB p50 or p52 is required in osteoclasts and their precursors, rather than osteoblasts, for IL-1-mediated bone resorption.
白细胞介素（IL）-1与绝经后和炎症介导的骨质流失有关。其表达受核因子κB（NF-κB）调控，反之亦然。为了研究NF-κB p50和p52（它们在胚胎发育过程中对破骨细胞形成是必需的）在IL-1诱导的骨吸收中的作用，我们使用了各种NF-κB基因敲除（KO）小鼠，包括p50-/-和p52-/-单基因敲除、p50-/-和p52+/-（3/4KO）以及p50-/-和p52-/-双基因敲除（dKO）小鼠。IL-1可增加野生型（wt）、p50和p52单基因敲除小鼠的血钙和骨吸收，但在3/4KO或dKO小鼠中则不然。与用IL-1处理的单基因敲除和wt小鼠相比，3/4KO小鼠骨髓培养物中的破骨细胞形成受损。wt和dKO小鼠的集落形成单位-粒细胞巨噬细胞（CFU-GM）集落细胞中IL-1受体表达相似。然而，IL-1促进了wt小鼠脾细胞来源的CFU-GM集落形成和存活以及这些集落产生的破骨细胞的形成、活性和存活，但dKO脾细胞来源的则不然。在wt和dKO小鼠的成骨细胞中，未观察到破骨细胞调节细胞因子、核因子κB受体活化因子配体（RANKL）和骨保护素（OPG）表达的差异。因此，对于IL-1介导的骨吸收，破骨细胞及其前体细胞而非成骨细胞中需要NF-κB p50或p52的表达。
