Huang Yuanqing, Chen Ning, Miao Dengshun
Department of Stomatology, Hunan University of MedicineHuaihua 418000, Hunan, People's Republic of China.
Institute of Stomatology, Nanjing Medical UniversityNanjing, Jiangsu, People's Republic of China.
Am J Transl Res. 2018 Jan 15;10(1):40-53. eCollection 2018.
To investigate whether pyrroloquinoline quinine (PQQ) plays an important role in rescuing Bmi-1 mice induced developmental disorders of teeth and mandible by regulating oxidative stress. We fed Bmi-1 mice a diet supplemented with PQQ (BKO+PQQ), BKO mice with normal diet (BKO) and wild type mice with normal diet (WT) as controls. We compared the differences of dental, mandibular phenotype by means of X-ray photography, micro CT scanning and three-dimensional reconstruction, HE staining, histochemistry, immunoistohemistry, TUNEL staining, Western blot and Flow cytometry in three groups of animals. Results showed that BKO+PQQ mice increased morphology of teeth and mandible, decreased X-ray transmittance, and increased bone density compared with BKO mice. Results also showed that the teeth volume and the dentin sialoprotein (DSP) immunopositive areas, the cortical thickness, alveolar bone volume, osteoblast number and activity, and alkaline phosphatase (ALP), Osteocalcin (OCN) and type I collagen (Col 1) were all reduced significantly in BKO mice compared with their wild-type littermates, whereas these parameters were increased significantly in BKO+PQQ mice compared with BKO mice. Our study indicated that, compared BKO mice, PCNA positive cells percentage of mandibular first molar epithelial root sheath area significantly increased in BKO+PQQ mice, and TUNEL positive cells percentage was significantly decreased. Further studies showed that supplemental PQQ played a role in anti-osteoporosis of teeth and mandible by up-regulating anti-oxidant capacity, inhibiting oxidative stress and reducing DNA damage, down-regulating CDKI proteins levels, and decreasing cell apoptosis. This study demonstrated that PQQ played an important role in rescuing mandible osteoporosis and disorder of teeth development in BKO mice by promoting osteoblastic bone formation of mandibular alveolar bone, inhibiting osteoclastic bone resorption, promoting odontoblast cell proliferation of epithelial root sheath area, inhibiting cell apoptosis, scavenging ROS.
为了研究吡咯喹啉醌（PQQ）是否通过调节氧化应激在挽救Bmi-1小鼠诱导的牙齿和下颌骨发育障碍中发挥重要作用。我们给Bmi-1小鼠喂食补充有PQQ的饮食（BKO+PQQ），给BKO小鼠喂食正常饮食（BKO），并给野生型小鼠喂食正常饮食（WT）作为对照。我们通过X射线摄影、显微CT扫描和三维重建、HE染色、组织化学、免疫组织化学、TUNEL染色、蛋白质免疫印迹法和流式细胞术比较了三组动物牙齿、下颌骨表型的差异。结果显示，与BKO小鼠相比，BKO+PQQ小鼠的牙齿和下颌骨形态得到改善，X射线透射率降低，骨密度增加。结果还显示，与野生型同窝小鼠相比，BKO小鼠的牙齿体积、牙本质涎蛋白（DSP）免疫阳性区域、皮质厚度、牙槽骨体积、成骨细胞数量和活性以及碱性磷酸酶（ALP）、骨钙素（OCN）和I型胶原蛋白（Col 1）均显著降低，而与BKO小鼠相比，BKO+PQQ小鼠的这些参数显著增加。我们的研究表明，与BKO小鼠相比，BKO+PQQ小鼠下颌第一磨牙上皮根鞘区域的增殖细胞核抗原（PCNA）阳性细胞百分比显著增加，TUNEL阳性细胞百分比显著降低。进一步研究表明，补充PQQ通过上调抗氧化能力、抑制氧化应激和减少DNA损伤、下调细胞周期蛋白依赖性激酶抑制蛋白（CDKI）水平以及减少细胞凋亡，在牙齿和下颌骨的抗骨质疏松中发挥作用。本研究表明，PQQ通过促进下颌牙槽骨的成骨细胞骨形成、抑制破骨细胞骨吸收、促进上皮根鞘区域的成牙本质细胞增殖、抑制细胞凋亡、清除活性氧，在挽救BKO小鼠下颌骨骨质疏松和牙齿发育障碍中发挥重要作用。
