Ameloblastin Function in Periodontal Development

描述（由申请人提供）： 哺乳动物的牙周组织是一种独特的支持结构，通过提供牢固的附着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300倍（Holliday et al. 2005，Luan et al. 2007）。此外，我们已经将AMBN定位在Hertwig上皮根鞘（HERS）中，并揭示了AMBN对PDL矿化和溶液和凝胶中晶体形成的抑制作用。我们的K14启动子驱动的AMBN过表达转基因小鼠模型具有稳健的牙周表型，与野生型对照相比，牙根牙骨质表面结构、颈部牙槽骨高度、牙周韧带宽度和釉质结构发生变化。我们的研究结果得到了临床研究的证实，这些研究显示了釉基质衍生物（EMD）对预防关节强直的积极作用（Iqbal和Bamaas 2001，Filippi et al. 2001），并且成釉蛋白和釉原蛋白基因敲除模型显示了PDL过度钙化的证据（Alamomoto et al. 2004，Hatakeyama et al. 2006）。总之，这些初步研究提供了一个研究计划，我们将解决的问题，AMBN是否是一个独特的HERS产品参与牙周发育和矿物质稳态的基础。拟议的研究旨在探索和开发新的临床援助，以造福数百万美国人患有牙周病。 公共卫生相关性：牙龈最独特的特征之一是牙根与颌骨的弹性但牢固的附着。在这里，我们将进行一系列的研究，以调查一个独特的基因产物（称为成釉蛋白）在牙齿附着形成的影响。这些研究可能最终导致牙龈疾病的新疗法。

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.