Ameloblastin Function in Periodontal Development

描述(申请人提供)：哺乳动物牙周组织是一种独特的支持结构，通过提供牢固的附着性和对压力的弹性反应，将牙齿固定在颌骨中。牙周组织的许多弹性特性是由连接牙根表面和牙槽骨的非矿化牙周膜(PDL)促进的。我们实验室最近的研究表明，成釉蛋白(AMBN)在牙周重塑过程中上调了300倍(Holliday等人)。2005年，Luan et al.2007)。此外，我们还将AMBN定位于Hertwig‘s上皮根鞘(HERS)，揭示了AMBN对溶液和凝胶中PDL矿化和晶体形成的抑制作用。与野生型对照相比，我们的K14启动子驱动、AMBN过表达的转基因小鼠模型具有强大的牙周表型，与野生型对照相比，牙周牙骨质表面结构、颈部牙槽骨高度、牙周膜宽度和釉质结构发生了变化。临床研究表明牙釉质基质衍生物(EMD)在预防强直方面有积极作用，这一发现得到了临床研究的支持(Iqbal和Bamaas 2001，Filippi等人)。2001)和成釉蛋白和成釉蛋白基因敲除模型显示PDL高钙化的证据(Fukomoto等人。2004年，HataKeyama等人。2006)。总之，这些初步研究为研究计划提供了基础，在该计划中，我们将解决AMBN是否是她参与牙周发育和矿物质动态平衡的独特产品的问题。拟议的研究旨在探索和开发新的临床辅助手段，以造福数百万患有牙周病的美国人。 与公共健康相关：牙胶最独特的特征之一是牙根弹性但牢固地附着在颌骨上。在这里，我们将进行一系列研究，以探讨一种独特的基因产物(称为成釉蛋白)在牙齿附着形成中的作用。这些研究可能最终会导致牙周病的新疗法。

DESCRIPTION (provided by applicant): The mammalian periodontium is a unique support structure that anchors teeth in the jaw bone by providing firm attachment and resilient responsiveness to pressures. Much of the resilient properties of the periodontium are facilitated by a non-mineralized periodontal ligament (PDL) that connects the root surface with the alveolar bone. Recent studies from our laboratory have suggested that ameloblastin (AMBN) was 300-fold upregulated during periodontal remodeling (Holliday et al. 2005, Luan et al. 2007). In addition, we have localized AMBN in Hertwig's Epithelial Root Sheath (HERS) and revealed an inhibitory effect of AMBN on PDL mineralization and crystal formation in solution and gels. Our K14 promoter-driven, AMBN overexpressing transgenic mouse model featured a robust periodontal phenotype with changes in root cementum surface structure, cervical alveolar bone height, periodontal ligament width, and altered enamel structure compared to wild-type controls. Our findings were underscored by clinical studies that have shown a positive effect of enamel matrix derivatives (EMD) on the prevention of ankylosis (Iqbal and Bamaas 2001, Filippi et al. 2001) and by ameloblastin and amelogenin gene knockout models displaying evidence of PDL hypercalcification (Fukomoto et al. 2004, Hatakeyama et al. 2006). Together, these preliminary studies provide the basis for a research plan in which we will address the question whether AMBN is a unique HERS product involved in periodontal development and mineral homeostasis. Proposed studies are designed to explore and develop novel clinical aids to the benefit of Millions of Americans suffering from periodontal disease. PUBLIC HEALTH RELEVANCE: One of the most unique features of tooth gums is the elastic but firm attachment of tooth roots to the jaw bone. Here we will conduct a series of studies to investigate the effect of a unique gene product (called ameloblastin) in the formation of tooth attachment. These studies might eventually lead to novel cures for gum diseases.