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Ameloblastin Function in Periodontal Development

成釉细胞在牙周发育中的功能

基本信息

批准号：
8089487
负责人：
Xianghong Luan
金额：
$ 36.94万
依托单位：
UNIVERSITY OF ILLINOIS AT CHICAGO
依托单位国家：
美国
项目类别：
财政年份：
2008
资助国家：
美国
起止时间：
2008-08-01 至 2013-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8089487
关键词：
Address Affect American Animal Model Ankylosis Biological Assay Breeding Candidate Disease Gene Cell physiology Cells Cervical Clinical Clinical Research Crystal Formation Crystallization Dental Cementum Dental Enamel Development Disease Down-Regulation Epithelial Gel Gene Expression Genes Height Homeostasis Immunohistochemistry In Situ Hybridization In Vitro Jaw Knockout Mice Laboratories Lead Minerals Modeling Morphogenesis Mus Mutant Strains Mice Osteoclasts Periodontal Diseases Periodontal Ligament Periodontium Phenotype Plant Roots Prevention Principal Investigator Property Proteins Research Research Design Reverse Transcriptase Polymerase Chain Reaction Role Series Solutions Structure Surface Testing Time Tissues Tooth root structure Tooth structure Transgenic Animals Transgenic Mice Validation Width alveolar bone amelogenin base biomineralization bone cell behavior design gene function in vivo knockout animal knockout gene loss of function mineralization mouse model nanoscale novel overexpression pressure programs promoter public health relevance research study

项目摘要

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.

描述（由申请人提供）：哺乳动物牙周组织是一种独特的支撑结构，通过提供牢固的附着力和对压力的弹性响应，将牙齿锚定在颌骨中。连接牙根表面和牙槽骨的非矿化牙周韧带（PDL）促进了牙周组织的大部分弹性特性。我们实验室最近的研究表明，在牙周重塑过程中，成釉素 (AMBN) 上调了 300 倍（Holliday 等人，2005 年；Luan 等人，2007 年）。此外，我们将 AMBN 定位于赫特维希上皮根鞘 (HERS) 中，并揭示了 AMBN 对溶液和凝胶中 PDL 矿化和晶体形成的抑制作用。我们的 K14 启动子驱动、AMBN 过表达转基因小鼠模型具有强大的牙周表型，与野生型对照相比，牙骨质表面结构、颈牙槽骨高度、牙周膜宽度和牙釉质结构发生变化。临床研究强调了我们的发现，这些研究表明牙釉质基质衍生物 (EMD) 对预防关节强直具有积极作用（Iqbal 和 Bamaas 2001，Filippi 等人 2001），成釉细胞和釉原蛋白基因敲除模型显示 PDL 过度钙化的证据（Fukomoto 等人 2004，Hatakeyama 等人 2006）。总之，这些初步研究为研究计划提供了基础，我们将在该计划中解决 AMBN 是否是涉及牙周发育和矿物质稳态的独特 HERS 产品的问题。拟议的研究旨在探索和开发新型临床辅助工具，造福数百万患有牙周病的美国人。公共健康相关性：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，我们将进行一系列研究来调查一种独特的基因产物（称为成釉素）在牙齿附着形成中的作用。这些研究最终可能会带来治疗牙龈疾病的新方法。