TCDD诱发牙根发育不良疾病的致病机制研究

项目名称： TCDD诱发牙根发育不良疾病的致病机制研究

项目编号： No.81072273

项目类型： 面上项目

立项/批准年度： 2011

项目学科： 生物科学

项目作者： 轩昆

作者单位： 中国人民解放军第四军医大学

项目金额： 10万元

中文摘要： 二噁英是一类危害极大的环境污染物，发育期的牙齿被认为是二噁英慢性毒性损害的生物标志。儿童时期二噁英的接触导致牙齿发育异常发病率较高，轻症可致牙釉质发育不全及牙冠变小，重症可致牙根发育不良（HTR）及缺牙。探讨二噁英对牙根发育的影响机制，可为临床医生提供其毒性反应预警信息，防止发育器质性损害而导致牙齿缺失。本项目发现TCDD可以导致牙根形态异常和矿化不全等牙根发育不良病理表现，影响牙根牙本质、牙骨质/牙周组织的形态发生和矿化形成。进而观察到TCDD对体外培养根端牙乳头干细胞SCAP细胞具有明显的抑制增殖和促进凋亡作用，并且影响其定向分化能力，抑制其分化形成牙根组织结构。最后初步证明TCCD可以介导AHR-EGFR信号通路调控牙根发育的功能基因，进而影响牙根发育相关细胞，最终导致牙根发育不良的病理表现。本研究结果为TCCD毒性的评估及牙根发育不良的致病因素研究增添新的信息，为环境污染导致牙齿发育异常疾病的预防和治疗提供新的实验依据和诊疗思路。

中文关键词： 二噁英；牙根发育不良；根尖牙乳头干细胞；发育期根端复合体；

英文摘要： Dioxins is one of the harmful environmental pollutants, and developing teeth are the biomarker of dioxin exposure. Developmental tooth defects, such as enamel dysplasia, crown deformation, hypoplasia of teeth roots and missing permanent teeth, have been reported in a normal child population exposed to dioxins. To explore the mechanism about the effects of dioxins on teeth roots development will provide the risk warning about dioxins toxicity for clinicians, and be conductive to prevent the occurrence of developmental organic harms such as teeth missing. In our projects, we found that 2,3,7,8-Tetrachlorodibenzo-p- dioxin(TCDD)could have the negative effects on morphogenesis and mineralization of dentin and cementum resulted in hypoplasia of teeth root.Then we found that TCDD could inhibit the proliferation and induce the apoptosis of stem cells from apical papilla (SCAP),moreover influence the differentiation of SCAP into root tissue.Finally, we confirmed that AHR-EGFR pathways could be activated by TCCD,which lead to pathological expressions of abnormal root formation by regulating the biological function of developing apical complex.Our results provided new informations about the toxicology evaluation of TCCD and the causative factors of short root anomaly.This project will offer new experimental evidences and strategies for the prevention and therapy of dental dysplasia induced by environmental pollution.

英文关键词： Dioxins;hypoplasia of teeth roots; stem cells from apical papilla; developing apical complex;