Biochemistry Division, National Cancer Center Research Institute 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, Japan.
Department of Oral and Maxillofacial Surgery, School of Dental Medicine, Tsurumi University 2-1-3 Tsurumi, Tsurumi-ku, Yokohama, Kanagawa 230-8501, Japan.
Cells. 2019 Sep 27;8(10):1157. doi: 10.3390/cells8101157.
Poly(ADP-ribose) polymerase (Parp)-1 catalyzes polyADP-ribosylation using NAD and is involved in the DNA damage response, genome stability, and transcription. In this study, we demonstrated that aged mouse incisors showed more frequent dental dysplasia in both ICR/129Sv mixed background and C57BL/6 strain compared to aged incisors, suggesting that Parp-1 deficiency could be involved in development of dental dysplasia at an advanced age. Computed tomography images confirmed that dental dysplasia was observed at significantly higher incidences in mice. The relative calcification levels of incisors were higher in both enamel and dentin ( < 0.05). Immunohistochemical analysis revealed (1) Parp-1 positivity in ameloblasts and odontoblasts in incisor, (2) weaker dentin sialoprotein positivity in dentin of incisor, and (3) bone sialoprotein positivity in dentin of incisor, suggesting ectopic osteogenic formation in dentin of incisor. These results indicate that Parp-1 deficiency promotes odontogenic failure in incisors at an advanced age. Parp-1 deficiency did not affect dentinogenesis during the development of mice, suggesting that Parp-1 is not essential in dentinogenesis during development but is possibly involved in the regulation of continuous dentinogenesis in the incisors at an advanced age.
聚（ADP-核糖）聚合酶 1（Parp-1）使用 NAD 催化多 ADP-核糖基化，参与 DNA 损伤反应、基因组稳定性和转录。在这项研究中，我们证明与老年相比，在 ICR/129Sv 混合背景和 C57BL/6 品系的老年小鼠切牙中，更频繁地出现牙齿发育不良，表明 Parp-1 缺陷可能参与高龄时牙齿发育不良的发生。计算机断层扫描图像证实，在 小鼠中观察到牙齿发育不良的发生率显著更高。与老年相比，切牙的相对钙化水平在釉质和牙本质中均升高（<0.05）。免疫组织化学分析显示（1）老年切牙中成釉细胞和成牙本质细胞中 Parp-1 阳性，（2）老年切牙牙本质中牙本质涎磷蛋白阳性减弱，（3）老年切牙牙本质中骨涎磷蛋白阳性，表明牙本质中异位成骨形成。这些结果表明 Parp-1 缺陷促进高龄时切牙的牙源性失败。Parp-1 缺陷不影响小鼠发育过程中的牙本质生成，表明 Parp-1 在发育过程中牙本质生成不是必需的，但可能参与高龄时切牙中连续牙本质生成的调节。
