Bmi1 regulate tooth and mandible development by inhibiting p16 signal pathway.
Bmi1 regulate tooth and mandible development by inhibiting p16 signal pathway.
复制标题
Bmi1通过抑制p16信号通路调节牙齿和下颌骨发育
DOI：
10.1111/jcmm.16468
复制
发表时间：
2021-05
影响因子：
5.3
通讯作者：
Hu Q
中科院分区：
文献类型：
--
作者：
Yin Y;Zhou N;Zhang H;Dai X;Lv X;Chen N;Miao D;Hu Q
为了确定p16的缺失是否可以纠正Bmi 1缺陷引起的牙齿和下颌骨生长迟缓，我们比较了纯合子p16缺陷（p16−/−）小鼠、纯合子Bmi 1缺陷（Bmi 1 −/−）小鼠、双纯合子Bmi 1和p16缺陷小鼠的牙齿和下颌骨表型。（Bmi 1 −/−p16−/−）小鼠与其野生型同窝小鼠在4周龄时通过放射照相、组织化学和免疫组织化学进行比较。结果显示，与Bmi 1 −/−小鼠相比，Bmi 1 −/−p16−/−小鼠的牙体密度、牙体体积和牙本质涎蛋白免疫阳性面积增加，而前牙本质面积占牙本质总面积的比值和双糖蛋白聚糖免疫阳性面积占牙本质面积的比值降低。这些结果表明，p16的缺失可以改善Bmi 1基因敲除小鼠的牙齿发育。与Bmi 1 −/−小鼠相比，Bmi 1 −/−p16−/−小鼠下颌骨骨密度、皮质厚度、牙槽骨体积、成骨细胞数量和活性、碱性磷酸酶阳性面积均显著增加。这些结果表明，p16的缺失可以改善Bmi 1基因敲除小鼠下颌骨的生长。此外，与野生型小鼠相比，p16−/−小鼠中细胞周期蛋白D、CDK 4和p53的蛋白表达水平显著升高; Bmi 1 −/−小鼠中细胞周期蛋白D和CDK 4的蛋白表达水平显著降低，而p27和p53的蛋白表达水平显著升高;与Bmi 1 −/−小鼠相比，Bmi 1 −/−p16−/−小鼠中的这些参数部分得到挽救。因此，我们的研究结果表明，Bmi 1通过抑制启动进入细胞周期的p16信号通路在调节牙齿和下颌骨发育中发挥作用。
To determine whether the deletion of p16 can correct tooth and mandible growth retardation caused by Bmi1 deficiency, we compared the tooth and mandible phenotypes of homozygous p16‐deficient (p16−/−) mice, homozygous Bmi1‐deficient (Bmi1−/−) mice, double homozygous Bmi1 and p16‐deficient (Bmi1−/−p16−/−) mice to those of their wild‐type littermates at 4 weeks of age by radiograph, histochemistry and immunohistochemistry. Results showed that compared to Bmi1−/− mice, the dental mineral density, dental volume and dentin sialoprotein immunopositive areas were increased, whereas the ratio of the predentin area to total dentin area and that of biglycan immunopositive area to dentin area were decreased in Bmi1−/−p16−/− mice. These results indicate that the deletion of p16 can improve tooth development in Bmi1 knockout mice. Compared to Bmi1−/− mice, the mandible mineral density, cortical thickness, alveolar bone volume, osteoblast number and activity, alkaline phosphatase positive area were all increased significantly in Bmi1−/−p16−/− mice. These results indicate that the deletion of p16 can improve mandible growth in Bmi1 knockout mice. Furthermore, the protein expression levels of cyclin D, CDK4 and p53 were increased significantly in p16−/− mice compared with those from wild‐type mice; the protein expression levels of cyclin D and CDK4 were decreased significantly, whereas those of p27 and p53 were increased significantly in Bmi1−/− mice; these parameters were partly rescued in Bmi1−/−p16−/− mice compared with those from Bmi1−/− mice. Therefore, our results indicate that Bmi1 plays roles in regulating tooth and mandible development by inhibiting p16 signal pathway which initiated entry into cell cycle.
登录
查看更多内容
影响因子：
4.3
作者：
Fischer, Nicholas W.;Prodeus, Aaron;Gariepy, Jean
通讯作者：
Gariepy, Jean
人 p16 启动子内 Bmi-1 响应元件的鉴定和表征
影响因子：
4.8
作者：
Meng, Sha;Luo, Min;Lu, Zhigang
通讯作者：
Lu, Zhigang
间充质干细胞自我更新和细胞命运决定的缺陷导致 Bmi-1 无效小鼠出现骨质减少表型
影响因子：
6.2
作者：
Zhang, Heng-Wei;Ding, Jiong;Miao, Dengshun
通讯作者：
Miao, Dengshun
体重指数缺乏会导致氧化应激和椎间盘退变，可通过抗氧化治疗缓解
影响因子：
5.3
作者：
Zhang, Qunhu;Li, Jie;Ren, Yongxin
通讯作者：
Ren, Yongxin
P16(INK4a) 缺失可改善 Bmi-1 缺陷的应激诱导过早衰老模型中的肾小管间质损伤
影响因子：
4.6
作者：
Jin J;Tao J;Gu X;Yu Z;Wang R;Zuo G;Li Q;Lv X;Miao D
通讯作者：
Miao D