Defective nuclear factor-κB-inducing kinase in aly/aly mice prevents bone resorption induced by local injection of lipopolysaccharide
Defective nuclear factor-κB-inducing kinase in aly/aly mice prevents bone resorption induced by local injection of lipopolysaccharide
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DOI：
10.1111/j.1600-0765.2010.01333.x
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发表时间：
2011-04-01
影响因子：
3.5
通讯作者：
Ohya, K.
中科院分区：
文献类型：
--
作者：
Soysa, N. S.;Alles, N.;Ohya, K.
背景与目的：核因子κ B （nf - κ B）在包括牙周炎在内的许多疾病的炎症部位被激活。核因子κ B诱导促炎细胞因子的转录，导致破骨细胞生成和骨吸收增加。最近，研究表明nf - κ B替代通路对维持骨生理稳态很重要。该途径的激活是通过核因子- κ b诱导激酶（NIK）将抑制剂p100加工成活性亚基p52。在体内和体外，aly/aly小鼠（NIKaly）中有缺陷的NIK会导致轻度骨质疏松和rankl刺激的破骨细胞发生变钝，这表明NIK对于基础和受刺激的破骨细胞发生是必要的。然而，NIK在病理性骨吸收中的作用尚未得到很好的研究。本研究采用aly/aly小鼠研究NIK在脂多糖（LPS）诱导的炎症性骨吸收中的作用。材料与方法：在小鼠颅骨上注射LPS， 5 d后处死。颅骨进行放射学分析。对组织切片进行抗酒石酸酸性磷酸酶染色，并进行组织形态学分析以量化破骨细胞的数量和骨吸收面积。结果：野生型和aly/+小鼠均有脂多糖诱导的炎症反应，aly/aly小鼠无脂多糖诱导的炎症反应。脂多糖显著降低了野生型和aly/+小鼠的颅骨骨密度，而LPS和载药注射的aly/aly小鼠的骨密度相当。此外，aly/aly小鼠对lps诱导的骨吸收和破骨细胞生成具有抗性。结论：综上所述，这些数据表明NIK在炎症的骨破坏成分中是重要的，并且代表了一个可能的治疗靶点。
Background and Objective:Nuclear factor-kappa B (NF-kappa B) is activated at sites of inflammation in many diseases, including periodontitis. Nuclear factor-kappa B induces the transcription of proinflammatory cytokines, resulting in increased osteoclastogenesis and bone resorption. Recently, it has been shown that the NF-kappa B alternative pathway is important for maintainance of physiological bone homeostasis. Activation of this pathway is by processing of the inhibitor p100 into the active subunit p52 by nuclear factor-kappa B-inducing kinase (NIK). Defective NIK in aly/aly mice (NIKaly) causes mild osteopetrosis and blunted RANKL-stimulated osteoclastogenesis in vivo and in vitro, suggesting that NIK is necessary for basal and stimulated osteoclastogenesis. Nevertheless, the role of NIK in pathological bone resorption is not well investigated. The present study was undertaken to investigate the role of NIK in lipopolysaccharide (LPS)-induced inflammatory bone resorption using aly/aly mice.Material and Methods:Mice were injected with LPS over the calvariae and killed 5 d later. Calvariae were subjected to radiological analysis. Histological sections were stained for tartrate-resistant acid phosphatase, and histomorphometric analysis was performed to quantify the number of osteoclasts and the area of bone resorption.Results:Lipopolysaccharide-induced inflammation was observed in wild-type and aly/+ mice but not in aly/aly mice. Lipopolysaccharide significantly reduced the calvarial bone mineral density in wild-type and aly/+ mice, whereas bone mineral density was comparable in LPS- and vehicle-injected aly/aly mice. In addition, aly/aly mice were resistant to LPS-induced bone resorption and osteoclastogenesis.Conclusion:Taken together, these data show that NIK is important in the bone-destructive components of inflammation and represents a possible therapeutic target.