Yin Ying, Wang Qun, Sun Wen, Wang Yuli, Chen Ning, Miao Dengshun
Institute of Stomatology, Nanjing Medical University, Nanjing, China; State Key Laboratory of Reproductive Medicine, The Research Center for Bone and Stem Cells, Department of Anatomy Histology and Embryology, Nanjing Medical University, Nanjing, China.
Clin Exp Pharmacol Physiol. 2014 Oct;41(10):807-16. doi: 10.1111/1440-1681.12276.
To assess the role of p27(kip1) in regulating dental formation and alveolar bone development, we compared the teeth and mandible phenotypes of homozygous p27(kip1) -deficient (p27(-/-) ) mice with their wild-type littermates at 2 weeks of age. At 2 weeks of age, dental mineral density, dental volume and dentin sialoprotein-immunopositive areas were increased significantly, whereas the predentin area : total dentin area and biglycan-immunopositive area : dentin area ratios were decreased significantly in p27(-/-) mice compared with their wild-type (WT) littermates. Mandible mineral density, cortical thickness, alveolar bone volume, type I collagen and osterix-immunopositive areas, osteoblast number and activity and mRNA expression of Runt-related transcription factor 2 (Runx2), alkaline phosphatase (ALP), osteocalcin and bone morphogenetic protein (bmp2) were all significantly increased in the mandibles, as was the number and surface of tartrate-resistant acid phosphatase-positive osteoclasts in the alveolar bone of p27(-/-) mice compared with their WT littermates. Furthermore, the percentage of proliferating cell nuclear antigen-positive cells in Hertwig's epithelial root sheath and protein expression of cyclin E and cyclin-dependent kinase 2 were increased significantly in p27(-/-) mice relative to their WT littermates. The results from this study indicate that p27 plays a negative regulatory role in dentin formation and alveolar bone development.
为了评估p27(kip1)在调节牙齿形成和牙槽骨发育中的作用，我们比较了2周龄纯合p27(kip1)缺陷（p27(-/-)）小鼠与其野生型同窝仔鼠的牙齿和下颌骨表型。在2周龄时，与野生型（WT）同窝仔鼠相比，p27(-/-)小鼠的牙齿矿物质密度、牙齿体积和牙本质涎蛋白免疫阳性面积显著增加，而前期牙本质面积与总牙本质面积之比以及双糖链蛋白聚糖免疫阳性面积与牙本质面积之比则显著降低。p27(-/-)小鼠下颌骨的矿物质密度、皮质厚度、牙槽骨体积、I型胶原蛋白和osterix免疫阳性面积、成骨细胞数量和活性以及Runt相关转录因子2（Runx2）、碱性磷酸酶（ALP）、骨钙素和骨形态发生蛋白（bmp2）的mRNA表达均显著增加，与WT同窝仔鼠相比，p27(-/-)小鼠牙槽骨中抗酒石酸酸性磷酸酶阳性破骨细胞的数量和表面积也增加。此外，相对于WT同窝仔鼠，p27(-/-)小鼠赫特维希上皮根鞘中增殖细胞核抗原阳性细胞的百分比以及细胞周期蛋白E和细胞周期蛋白依赖性激酶2的蛋白表达显著增加。本研究结果表明，p27在牙本质形成和牙槽骨发育中起负调节作用。
