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：
7840797
负责人：
Xianghong Luan
金额：
$ 1.35万
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：
2009
资助国家：
美国
起止时间：
2009-06-01 至 2010-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7840797
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 Mice Transgenic Organisms 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）：哺乳动物牙周是一种独特的支撑结构，可通过为压力提供牢固的依恋和弹性的响应能力来固定颌骨的牙齿。牙周的许多弹性特性都是由将根表面与肺泡骨联系起来的非矿化牙周韧带（PDL）促进的。我们实验室的最新研究表明，在牙周重塑期间，阿素母细胞素（AMBN）上调了300倍（Holliday等，2005，Luan等，2007）。此外，我们在Hertwig的上皮根鞘（HERS）中局部局部化AMBN，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启动子驱动的AMBN过表达的转基因小鼠模型具有强大的牙周表型，与野生型对照组相比，根正面表面结构变化，颈牙牙性骨骼高度，牙周韧带宽度，牙周韧带宽度和搪瓷结构改变。我们的发现是由临床研究强调的，临床研究表明，牙釉质基质衍生物（EMD）对预防氧化强化（Iqbal and Bamaas 2001，Filippi等，2001）以及阿米他蛋白蛋白基因基因基因敲除模型，显示PDL超钙化证据（FukomaTo and al.2004）。这些初步研究共同为研究计划提供了基础，在该计划中，我们将解决AMBN是否是涉及牙周开发和矿物质稳态的独特产品。拟议的研究旨在探索和开发新颖的临床辅助工具，以使数百万患有牙周疾病的美国人受益。公共卫生相关性：牙齿牙龈最独特的特征之一是牙齿根部与下颌骨的固定。在这里，我们将进行一系列研究，以研究独特的基因产物（称为氨基细胞素）对牙齿固定的形成的影响。这些研究最终可能导致牙龈疾病的新颖治疗方法。