牙釉质发育缺陷性疾病的环境影响因素及临床管理

牙釉质形成是有赖于多层机制协同调控的复杂生理过程, 包括组织发生、形态发生、细胞分化等重要阶段, 最终由牙源性上皮细胞定向分化为功能性成釉细胞, 分泌基质并介导矿化。这一过程对各种局部和全身干扰因素非常敏感。牙发育与萌出过程始于胚胎阶段, 持续至青春期甚至成年后这一漫长时期, 各种干扰因素都可能使乳牙及恒牙的硬组织基质形成和矿化异常, 导致牙釉质发育缺陷性疾病。其中, 生命早期(从受精卵开始到8岁前)是对环境因素暴露最敏感的时期, 同时也是乳牙及恒牙牙釉质发育的关键时期, 这一时期的环境因素暴露往往导致不同程度的釉质发育缺陷。本文回顾了环境因素影响牙釉质发育缺陷性疾病的研究进展, 概述了环境因素导致牙釉质发育缺陷性疾病的遗传学及表观遗传学机制, 总结了针对该类疾病基于三级预防的临床管理策略, 以期为从生命早期关键时间窗口预防牙发育异常, 提供优生优育健康咨询及促进儿童口腔健康管理提供依据, 通过前移儿童口腔疾病的预防关口, 创建妇幼友好型社会, 提高新生人口素质。     

牙源性肿瘤的WHO(2005)新分类

由于牙源性肿瘤的发生与颌骨和牙发育关系密切,故在其发病、临床病理表现以及生物学行为等方面均具特殊性,是口腔颌面部特有的一类肿瘤,一直备受关注。上世纪40年代以前,几乎所有的牙源性肿瘤被统称为“牙瘤（odontome）”。1946年,Thoma和Goldmann按组织来源将牙源性肿瘤分为上皮性、间叶性和混合性三类,取消了笼统“牙瘤”的概念。基于牙源性肿瘤中可能存在类似于牙发育过程中上皮和间叶组织之间的相互诱导作用,     

Yes相关蛋白基因在牙发育中的作用

牙发育过程,包括胚胎早期预定成牙部位到发育形成完整的牙及牙周组织的发育成熟,是一个复杂的连续过程。牙发育实际上是牙源性上皮与脑神经嵴来源的牙源性间充质之间相互作用的结果,这一过程受到诸多信号的影响。Yes相关蛋白基因（YAP）是Hippo通路中的靶基因,在牙胚发育的初始阶段,可在不同部位检测到其表达。Hippo-YAP信号通路通过抑制YAP的活性,调控细胞增生和程序性细胞死亡间的平衡,从而调控器官的大小。本文就Hippo-YAP信号通路和YAP在牙发育过程中的表达等研究进展作一综述。     

中国儿童错𬌗畸形早期矫治专家共识

错𬌗畸形是世界卫生组织公布的口腔三大疾病之一,其发病率在我国有升高的趋势,严重影响我国近2.6亿儿童牙颌面功能、颜面美观及生长发育,甚至影响儿童全身及心理健康发育。错𬌗畸形发生涉及遗传及环境因素,早期矫治创建良好的牙颌面生长环境,纠正异常牙颌面生长、控制异常遗传因素,能有效地降低儿童错𬌗畸形的发病率,维护我国儿童身心健康,这是我国社会经济发展的迫切需要,具有重大的现实和社会意义。中国国家卫生健康委医院管理研究所“儿童早期矫治规范化诊疗项目”专家组撰写“中国儿童错𬌗畸形早期矫治专家共识”,旨在引导和普及我国儿童早期矫治临床治疗,促进我国儿童早期矫治理论与临床水平的提高,加速我国儿童早期矫治专业发展。共识阐述了错𬌗畸形的危害性及早期矫治的必要性,提出了儿童早期矫治的原则和基本内容。在遵循牙颌面发展规律的基础上,提出从孕期到恒牙列初期儿童牙颌面生长发育不同时期分阶段的预防与阻断治疗的指导性建议。错𬌗畸形早期矫治的推广和规范是一个系统工程,通过科学的、全面的分级医疗及专业培训将最终完善我国儿童早期矫治临床体系,达到全面呵护我国儿童牙颌面健康,提高我国儿童口腔健康及全身健康水平的目的。     

牙颌发育模式及分子机制

牙颌发育模式及分子机制是理解牙颌结构功能的前提，也是再生牙颌组织器官的基础。牙发育分为牙胚发育期、牙冠形成期和牙根形成期。在这一过程中，关键基因具有时间空间的序列性表达。牙源性上皮和间充质相互作用以及釉结等特殊细胞群对牙冠形态精细化、个性化调控，发育成牙。在生物应力、信号调控机制下，牙顺利萌出并发挥功能。牙和颌骨同处发育之中，相互独立又相互依存，相互调控共同发育成为一个有机的整体。牙和颌骨均起源于第一鳃弓，牙或颌骨的发育异常通常会导致彼此的发育缺陷。本文评述牙和颌骨发育的过程，首次阐述稳态微环境在牙发育中的作用以及重点关注颌骨发育中以梅克尔软骨为代表的典型结构和特殊的信号调控机制，提出牙颌一体化发育模式，动态解析牙和颌骨一体化发育过程，并期待未来将这些新模式和机制运用于组织再生。     

中国儿童错(牙合)畸形早期矫治专家共识

错(牙合)畸形是世界卫生组织公布的口腔三大疾病之一,其发病率在我国有升高的趋势,严重影响我国近2.6亿儿童牙颌面功能、颜面美观及生长发育,甚至影响儿童全身及心理健康发育.错(牙合)畸形发生涉及遗传及环境因素,早期矫治创建良好的牙颌面生长环境,纠正异常牙颌面生长、控制异常遗传因素,能有效地降低儿童错(牙合)畸形的发病率,...     

氟对牙发育影响作用的研究进展

氟是人体必需的微量元素,在机体和牙的发育过程中有着重要的作用。牙在发育过程中摄入过量的氟,将导致氟斑牙的发生。氟通过对矿化相关的基质、基质蛋白、蛋白酶、相关细胞以及离子跨膜转运等多种途径影响正常的牙矿化模式,造成牙的矿化异常。下面就氟对牙发育、釉基质、基质蛋白酶、成釉细胞、牙本质基质蛋白和蛋白聚糖的影响作用的研究进展作一综述。     

儿童常见牙病与错(牙合)畸形

龋病及其并发症、牙外伤、咬合紊乱、牙发育异常是儿童口腔科常见的就诊原因,儿童口腔临床工作不仅需要治疗儿童各种常见牙病,还需对其口腔健康进行管理,使其从第一颗乳牙萌出开始,顺利建立健康乳牙列、混合牙列,直至建立正常年轻恒牙列.儿童错(胎)畸形的发生不仅与遗传因素有关,儿童时期乳牙龋坏、牙髓根尖周疾病、牙外伤、不正确的喂养方式、不良饮食习惯等均可引起咬合紊乱与错(砑)畸形.本文从儿童龋病入手,讲述几种儿童常见牙病与错(验)畸形发生的关系,以期为儿童口腔专科医生及全科口腔医生进行系统化的儿童口腔健康管理提供依据.     

非综合征性先天缺牙相关基因的研究进展

先天缺牙是牙发育过程中的数目异常,包括个别牙先天缺失、多数牙先天缺失和先天无牙症。先天缺牙根据是否有伴发症状可分为综合征性和非综合征性,表现为常染色体的显性或隐性遗传、X-连锁遗传特性等。先天缺牙可以是有家族遗传史的,也可以是散发的。本文就与非综合征性先天缺牙有关的配对盒基因-9、肌节同源盒基因-1、轴抑制基因-2和外...     

炎症牙源性组织中的干细胞在牙周骨组织再生中的研究进展及应用前景

通过组织工程实现牙周骨组织再生是近年的研究热点。通常, 牙周组织工程的种子细胞来源于健康的牙源性组织, 但由于获得来源和拔牙适应证的限制, 健康牙源性干细胞的数量无法满足临床需求。炎症牙源性组织中的干细胞主要提取自炎症牙髓、根尖周及牙周组织, 具有较健康牙源性组织中的干细胞来源丰富、保留干细胞的部分基本特征等优点, 因而其有望应用于牙周骨组织再生领域。本文通过对炎症牙源性组织中的干细胞在牙周骨组织再生方面的应用现状及前景进行综述, 探讨该类细胞作为种子细胞的可行性, 以期为炎症牙源性组织中的干细胞研究及应用提供参考。     

Environmental factors in non-syndromic orofacial clefts: A review based on meta-analyses results

Non-syndromic orofacial clefts (NSOFCs) are prevalent birth defects with a complex etiology where several interacting genetic and environmental factors have been observed. This narrative review describes maternal exposures that have been significantly associated with protective effects or risk factors. The statistically significant information reported here was found in meta-analysis studies, taking advantage of their precision in defining intervention effects and their management of heterogeneity between studies. In addition, I propose a hypothesis explaining the biological basis for the results of the meta-analyses. This review aims to improve the evidence available in parent counseling, to prevent the occurrence of orofacial clefts by suggesting lifestyle changes.     

Developmental dental toxicity of dioxin and related compounds--a review

Non-halogenated polycyclic aromatic hydrocarbons (PAHs) and halogenated aromatic hydrocarbons such as polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs, or dioxins), and polychlorinated biphenyls (PCBs) are wide-spread environmental pollutants that have unequivocal adverse effects on different species, including humans. Accidental exposure of children to high amounts of PCDD/Fs has been found to be associated with developmental enamel defects and missing permanent teeth. An association between dioxin exposure via mother's milk and developmental mineralisation defects in permanent first molars was also found in otherwise healthy Finnish children born in the late 1980s but not in those born in the late 1990s. Results of experimental animal studies in vivo and in vitro are compatible with findings in human teeth. In addition to the dose, dental effects of the most toxic dioxin congener, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), essentially depend on the stage of tooth development at the time of exposure. Accordingly, TCDD arrests early rat and mouse molar tooth development and in more advanced teeth it interferes with mineralisation of enamel and dentine and arrests root development. Expression of the specific dioxin receptor (AhR) in dental cells at TCDD-sensitive stages of tooth development suggests that the dental, like other developmental effects of TCDD, are mediated by the AhR. Early effects also depend on the epidermal growth factor receptor and involve enhanced apoptosis. The lowest TCDD dose (30ng/kg) causing adverse dental effects in rats has been estimated to result in maternal tissue levels approaching the high end of human background range and human milk PCDD/F levels that were associated with enamel defects in children. However, because of the uniform and clear decline in background dioxin and PCB levels in mother's milk during the last twenty years, dioxins are currently likely to be of small or no account as regards developmental dental defects in children. Even so, this is not the case after heavy exposure and little is known about the possible synergistic effects of these toxicants with other chemicals interfering with tooth development.     

BMP4、TGF-β3基因多态性与环境暴露在非综合征性唇腭裂发生中的交互作用

目的 探讨环境暴露因素、骨形态生成蛋白4(BMP4)基因、转化生长因子β3(transforming growth factor beta-3,TGF-β3)基因之间的交互作用在非综合征性唇腭裂(nonsyndromic cleft lip and cleft palate,NSCLP)发生中的可能作用.方法 通过问卷调查获取环境暴露资料.用聚合酶链反应(PCR)-限制性片段长度多态性(restriction fragment length polymorphism,RFLP)技术对对照组(200例)和NSCLP组(200例)各基因位点的多态性进行检测.采用多因子降维法(multifactor djmensionality reduction,MDR)分析基因之间、基因与环境之间的交互作用关系,并对筛选的交互作用关系用Logistic回归进行验证.结果 BMP4 T538C、TGF-β3 C641A和TGF-β3G15572-三个单核苷酸多态性(single nucleotide polymorphism,SNP)位点间的交互作用与NSCLP的发生无关联.基因与环境交互作用分析发现,BMP4 T538C与母亲妊娠早期被动吸烟、母亲妊娠早期感染史对NSCLP的发生具有交互作用;TGF-β3G15572-与母亲妊娠早期被动吸烟、母亲妊娠早期感染史、父亲知晓妊娠前吸烟、父亲知晓妊娠前饮酒、母亲妊娠早期补充维生素对NSCLP的发生具有交互作用.经Logistic回归验证,结果一致.结论 NSCLP是基因与环境因素共同作用的结果,易感基因多态性影响着个体对环境因素的反应,研究它们之间的相互关系对阐明NSCLP的病因及发病机制具有重要意义.     

Multilevel complex interactions between genetic,epigenetic and environmental factors in the aetiology of anomalies of dental development

Dental anomalies are caused by complex interactions between genetic, epigenetic and environmental factors during the long process of dental development. This process is multifactorial, multilevel, multidimensional and progressive over time. In this paper the evidence from animal models and from human studies is integrated to outline the current position and to construct and evaluate models, as a basis for future work.Dental development is multilevel entailing molecular and cellular interactions which have macroscopic outcomes. It is multidimensional, requiring developments in the three spatial dimensions and the fourth dimension of time. It is progressive, occurring over a long period, yet with critical stages. The series of interactions involving multiple genetic signalling pathways are also influenced by extracellular factors. Interactions, gradients and spatial field effects of multiple genes, epigenetic and environmental factors all influence the development of individual teeth, groups of teeth and the dentition as a whole. The macroscopic, clinically visible result in humans is a complex unit of four different tooth types formed in morphogenetic fields, in which teeth within each field form directionally and erupt at different times, reflecting the spatio-temporal control of development.Even when a specific mutation of a single gene or one major environmental insult has been identified in a patient with a dental anomaly, detailed investigation of the phenotype often reveals variation between affected individuals in the same family, between dentitions in the same individual and even between different teeth in the same dentition. The same, or closely similar phenotypes, whether anomalies of tooth number or structure, may arise from different aetiologies: not only mutations in different genes but also environmental factors may result in similar phenotypes. Related to the action of a number of the developmental regulatory genes active in odontogenesis, in different tissues, mutations can result in syndromes of which dental anomalies are part. Disruption of the antagonistic balance between developmental regulatory genes, acting as activators or inhibitors can result in dental anomalies. There are critical stages in the development of the individual tooth germs and, if progression fails, the germ will not develop further or undergoes apoptosis. The reiterative signalling patterns over time during the sequential process of initiation and morphogenesis are reflected in the clinical association of anomalies of number, size and form and the proposed models.An initial step in future studies is to combine the genetic investigations with accurate recording and measurement of the phenotype. They also need to collate findings at each level and exploit the accurate definition of both human and murine phenotypes now possible.     

Dental enamel formation and its impact on clinical dentistry

The nature of tooth enamel is of inherent interest to dental professionals. The current-day clinical practice of dentistry involves the prevention of enamel demineralization, the promotion of enamel remineralization, the restoration of cavitated enamel where demineralization has become irreversible, the vital bleaching of dental enamel that has become discolored, and the diagnosis and treatment of developmental enamel malformations, which can be caused by environmental or genetic factors. On a daily basis, dental health providers make diagnostic and treatment decisions that are influenced by their understanding of tooth formation. A systemic condition during tooth development, such as high fever, can produce a pattern of enamel defects in the dentition. Knowing the timing of tooth development permits estimates about the timing of the disturbance. The process of enamel maturation continues following tooth eruption, so that erupted teeth can become less susceptible to decay over time. Mutations in the genes encoding enamel proteins lead to amelogenesis imperfecta, a collection of inherited diseases having enamel malformations as the predominant phenotype. Defects in the amelogenin gene cause X-linked amelogenesis imperfecta, and genes encoding other enamel proteins are candidates for autosomal forms. Here we review our current understanding of dental enamel formation, and relate this information to clinical circumstances where this understanding may be particularly relevant.     

Role of Matrix Gla protein in midface development: Recent advances

Craniofacial development is a delicate process that involves complex interactions among cells of multiple developmental origins, their migration, proliferation, and differentiation. Tissue morphogenesis of the craniofacial skeleton depends on genetic and environmental factors, and on specific signaling pathways, which are still not well understood. Developmental defects of the midface caused by the absence, delays, or premature fusion of nasal and maxillary prominences vary in severity; leading to clefts, hypoplasias, and midline expansion. In the current review, we focus on the importance of the chondrocranium in craniofacial growth and how its impaired development leads to midface hypoplasia. More importantly, we reported how Matrix Gla protein (MGP), a potent inhibitor of extracellular matrix mineralization, facilitates midface development by preventing ectopic calcification of the nasal septum. In fact, MGP may act as a common link in multiple developmental pathologies all showing midface hypoplasia caused by abnormal cartilage calcification. This brief review discusses the gap in knowledge in the field, raises pertinent questions, which remain unanswered, and sheds light on the future research directions.     

Environmental and heritable factors in the etiology of oral diseases--a population-based study of Swedish twins

A population-based twin study is a useful design for quantification of the effects of genes and environmental factors in disease etiology. We used data from 10,000 Swedish twin pairs to quantify genetic and environmental contributions to tooth loss and periodontal health. Oral health information was obtained from telephone interviews. Structural equation models measured the relative importance of genetic and environmental factors. Genetic factors contributed to 14% of variation in tooth loss among women, and 39% among men. Non-shared environmental factors accounted for one-quarter of risk; environmental factors shared by twins comprised the remainder. Heritability estimates of periodontal disease were 39% and 33% for women and men, respectively, while non-shared environmental factors accounted for the remaining variation. Heritability for both conditions varied as a function of age and smoking status. Analysis of data from this large, population-based study demonstrates a moderate role of genetic factors in oral diseases, and suggests potential gene-environment interactions.