Bmi-1基因在调节牙本质及牙槽骨形成和发育中的作用及机制研究

The effects and mechanism of Bmi-1 gene on the formation and development of teeth and alveolar bone

目的:研究B细胞淋巴瘤滤过性病毒插入位点1基因(Bmi-1)对小鼠牙本质及牙槽骨形成和发育的作用及机制。方法:3周龄Bmi-1基因敲除(BKO)小鼠15只给予普通饮食4周,取同窝野生型小鼠(WT)15只进行对照,通过影像学、组织病理学、分子生物学和细胞培养的方法比较分析两组动物之间的差异。结果:与WT小鼠相比,BKO小鼠牙量、牙本质涎磷蛋白(DSP)、皮质骨厚度、牙槽骨量、成骨细胞数、I型胶原蛋白(Col I)及骨钙素(OCN)均减少;而破骨细胞(TRAP)及双糖链蛋白多糖(Biglycan)较WT小鼠明显增多。3周龄牙槽骨骨髓间充质干细胞(BMSCs)体外培养结果发现,Bmi-1有利于BMSCs的形成和分化。结论:Bmi-1基因通过促进成骨细胞骨形成、抑制破骨细胞骨吸收以及刺激BMSCs的形成和分化调节牙本质发育及牙槽骨形成。

Objective:To study the effects and mechanism of B cell-specific moloney leukemia virus insert site-1 gene(Bmi-1)on the formation and development of dentin and alveolar bone in mice.Methods:All the 3-week weaning littermate mice were fed with normal diet for 4 weeks and then killed for further statistical analysis.Phenotypes of teeth and alveolar bone of mandible of Bmi-1 gene knockout(BKO)mice were compared with those of wild-type(WT)mice through image,histochemistry and immunohistochemistry,molecular biology and cell biology.Results:BKO mice had significantly reduced tooth volume,immunopositive area of dentin sialoprotein,cortical thickness,alveolar bone volume,number and activity of osteoblasts,alkaline phosphatase,type I collagen(Col I)and osteocalcin(OCN)compared with their wild-type littermates.However,osteoclasts(TRAP)and Biglycan were significantly increased compared with WT mice.In vitro culture of bone marrow mesenchymal stem cells(BMSCs)from 3-week-old WT and BKO mice,Bmi-1 has beneficial effects on CFU-F formation efficiency and differentiation of BMSCs in alveolar bone.Conclusion:Bmi-1 gene regulates dentin development and alveolar bone formation by promoting osteoblast bone formation,inhibiting osteoclast bone resorption,and stimulating BMSCs formation and differentiation.