国际口腔医学杂志

国际口腔医学杂志 ›› 2022, Vol. 49 ›› Issue (6): 641-647.doi: 10.7518/gjkq.2022103

• 论著 • 上一篇    下一篇

钙黏蛋白5驱动内皮细胞特异性过表达Dickkopf 1影响骨形成

尹一佳1(),杨瑾廷1,申建琪2,黄凌依1,井岩3,官秋玥4(),韩向龙1   

  1. 1.口腔疾病研究国家重点实验室;国家口腔疾病临床医学研究中心;四川大学华西口腔医院正畸科 成都 610041
    2.山西医科大学汾阳学院 吕梁 032299
    3.美国德克萨斯州农工大学贝勒牙科学院 达拉斯 TX 75246
    4.四川省人民医院草堂病区老年病房 成都 610072
  • 收稿日期:2022-02-01 修回日期:2022-07-15 出版日期:2022-11-01 发布日期:2022-11-03
  • 通讯作者: 官秋玥
  • 作者简介:尹一佳，学士，Email：yvonnist@163.com
  • 基金资助:
    四川省科技厅应用基础研究项目(2018JY0271)

Endothelial-cell-specific overexpression of Dickkopf 1 using Cadherin 5 promoter regulates osteogenesis in vivo

Yin Yijia1(),Yang Jinting1,Shen Jianqi2,Huang Lingyi1,Jing Yan3,Guan Qiuyue4(),Han Xianglong1   

  1. 1.State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases & Dept. of Orthodontics, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China
    2.Fenyang College of Shanxi Medical University, Lüliang 032299, China
    3.Baylor College of Dentistry, Texas A&M University, Dallas TX 75246, USA
    4.Geriatric Department, Caotang District, Sichuan Provincial People’s Hospital, Chengdu 610072, China
  • Received:2022-02-01 Revised:2022-07-15 Online:2022-11-01 Published:2022-11-03
  • Contact: Qiuyue Guan
  • Supported by:
    Applied Basic Research Program of Science & Technology Department of Sichuan Province(2018JY0271)

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摘要：

目的 通过检测体内内皮细胞特异性过表达Dickkopf 1（DKK1）对股骨和牙槽骨骨形成和血管形成的影响，为DDK1在正畸牙移动骨重建和血管形成中的作用提供依据。 方法 构建钙黏蛋白5（Cdh5）驱动的内皮细胞特异性DKK1过表达转基因小鼠（Cdh5-Cre；R26-DKK1/R26-DKK1），检测股骨和牙槽骨骨形态和骨量的变化。 结果 Cdh5-Cre；R26-DKK1/R26-DKK1小鼠的股骨和牙槽骨DKK1高表达，骨量增加，骨髓腔缩窄；股骨中Trap+细胞数目降低；股骨和牙槽骨中Ⅳ型胶原蛋白表达增加。 结论 DKK1可能调控正畸牙移动。Cdh5驱动内皮细胞中DKK1表达增加与骨组织中软骨细胞的分化及骨小梁的形成、牙周组织骨量的增加密切相关。

关键词: 内皮细胞, 骨形成, 股骨, 牙槽骨

Abstract:

Objective This study aimed to the expression of Dickkopf 1 (DKK1) during orthodontic tooth movement is examined. Then, the effects of endothelial-cell-specific overexpression of DKK1 on bone formation were detected. Moreover, the function of DKK1 on bone formation through endothelial cells was explained. Methods A rat orthodontic tooth movement model was constructed to detect the expression of DKK1 on the compressive and tensile side of alveolar bone. Then, R26-DKK1 and Cadherin 5 (Cdh5)-Cre mice were crossbred to produce transgenic mice expressing DKK1 in endothelial cells (Cdh5-Cre; R26-DKK1/R26-DKK1) and to detect the changes of bone morphology and bone volume of the femur and alveolar bone. Results During orthodontic tooth movement, DKK1 was highly expressed in the compressive side. DKK1 transgenic mice widely expressed DKK1 in the femur and alveolar bone, increased in bone density, narrowed in central bone marrow cavity, and increased in Trap+ cells numbers and collagen Ⅳ expression compared with wild type controls. Conclusion DKK1 might regulate orthodontic tooth movement. Endothelial-cell-specific overexpression of DKK1 using Cdh5 promoter is closely related to the differentiation of chondrocytes and the formation of trabecular bone, and causes increased expression level of collagen Ⅳ in periodontal tissue and bone.

Key words: endothelial cells, bone formation, femur, alveolar bone

中图分类号: 

  • R 782

图1

DKK1 Tg小鼠股骨和牙槽骨DKK1表达情况A：免疫组织化学显示，Dkk1 Tg小鼠股骨DKK1表达量，股骨生长板软骨-骨界面（黄色实线），软骨细胞DKK-1表达（白色箭头）；B：免疫组织化学显示，Dkk1 Tg小鼠牙周组织DKK1表达量，牙周膜（黄色实线内），DKK1表达（白色星形）。"

图 2

DKK1 Tg小鼠股骨及牙槽骨形态学和骨量改变A：Micro-CT示股骨远心端及牙槽骨骨量变化，*P<0.05，NS示P>0.05；B：HE染色示，股骨远心端形态学变化，股骨远心端生长板（黑色线段），肥大软骨细胞层（白色箭头）；C：HE染色示，牙槽骨形态学变化，密质骨（白色星），松质骨间髓腔（白色箭头）。"

图3

DKK1 Tg小鼠股骨破骨活性A：股骨Trap+染色（白色箭头）；B：股骨Trap+细胞计数。 *P<0.05。"

图 4

DKK1 Tg小鼠Col IV表达情况A：股骨Col Ⅳ表达量在生长板软骨-骨界面和肥大软骨细胞的表达（白色箭头）；B：下颌骨牙周膜中Col Ⅳ表达（白色星）。"

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