A novel IkB kinase inhibitor attenuates ligature-induced periodontal disease in mice
A novel IkB kinase inhibitor attenuates ligature-induced periodontal disease in mice
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DOI：
10.1111/jre.12615
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发表时间：
2019-04-01
影响因子：
3.5
通讯作者：
Izumi, Yuichi
中科院分区：
文献类型：
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作者：
Kure, Keitetsu;Sato, Hiroki;Izumi, Yuichi
背景与目的imd -0354是一种新型的IKK激酶抑制剂，具有调节炎症的作用。本研究的目的是研究该试剂对结扎性牙周炎骨质流失的影响。材料与方法将8周龄C57BL/6J小鼠右上颌第二磨牙周围结扎。在结扎前给小鼠腹腔注射IMD-0354。对照组小鼠在结扎前腹腔注射0.5%羧甲基纤维素（CMC）作为载体。为了确定该试剂对结扎性牙周炎小鼠的最佳浓度，我们初步研究了IMD-0354 1、5、10mg/kg三种浓度对结扎性牙周炎小鼠的影响。我们通过micro-CT分析确定10mg/kg为IMD组的最佳浓度后，将IMD组和CMC组（n=15，包括所有分析）分别细分为两个小组进行进一步分析：I组（IMD组未结扎侧）、IL组（IMD组结扎侧）、C组（CMC组未结扎侧）和CL组（CMC组结扎侧）。IMD组和CMC组小鼠每日各给药，结扎后8d处死。为了评估骨吸收，我们进行了显微ct和组织学分析。我们还进行了实时PCR检测促炎和骨代谢标志物。结果结扎后8d，试验组（IMD）与对照组（CMC）的线性骨丢失和体积参数差异有统计学意义。在牙龈组织mRNA表达水平方面，IMD组与CMC组相比，RANKL水平明显受到抑制。IMD-0354也倾向于抑制白细胞介素-1 β、肿瘤坏死因子α和骨保护素的水平。组织学分析显示，与CMC组相比，IMD组trap阳性多核细胞的相对数量明显减少。结论imd -0354对结扎性牙周炎骨吸收有调节作用，提示通过下调NF κ b抑制IKK可能为牙周患者预防或抑制牙周炎提供有效途径。
Backgrounds and ObjectivesIMD-0354 is a novel I kappa-B kinase (IKK) inhibitor, which regulates inflammation. The purpose of this study was to examine the effect of the reagent on bone loss for ligature-induced periodontitis.Material and MethodsWe ligated around the upper right second molars of 8-week-old C57BL/6J mice in the split-mouth model. The test mice were injected intraperitoneally with IMD-0354 before the placement of the ligature. The control mice were injected intraperitoneally with 0.5% carboxymethylcellulose (CMC) as vehicle before the placement of the ligature. To determine the optimum concentration of the reagent on ligature-induced periodontitis in the mice, we examined the effect of three types of concentration, which were 1, 5, and 10mg/kg of IMD-0354, as a preliminary experiment. After we determined 10mg/kg as the optimum concentration for the IMD group by micro-CT analysis, both the IMD and CMC groups (n=15 each in total, including all the analyses) were subdivided into two small groups, respectively, for further analyses: I group (unligated side of IMD group), IL group (ligated side of IMD group), C group (unligated side of CMC group) and CL group (ligated side of CMC group). The mice in the IMD and CMC groups were treated with each reagent daily and sacrificed 8days after the ligation. For assessment of bone resorption, we performed micro-CT and histological analyses. We also carried out real-time PCR to investigate proinflammatory and bone metabolic markers.ResultsThere were significant differences for linear bone loss and volumetric parameter in the test (IMD) group compared to the control (CMC) group 8days after ligation. In terms of the mRNA expression level of gingival tissue, the level of RANKL was significantly suppressed in the IMD group compared to the CMC group. IMD-0354 also tended to suppress the levels of interleukin-1 beta, tumor necrosis factor-alpha, and osteoprotegerin. For histological analysis, the relative numbers of TRAP-positive multinucleated cells decreased significantly in the IMD group compared to the CMC group.ConclusionIMD-0354 regulated bone resorption by ligature-induced periodontitis, and it is suggested that the inhibition of IKK via down-regulation of NF kappa-B may provide periodontal patients with an effective approach to prevent or suppress the disease.