Phosphate Modulation of Dental Tissues

牙齿组织的磷酸盐调节

基本信息

批准号：
7446131
负责人：
Martha J Somerman
金额：
$ 3.82万
依托单位：
UNIVERSITY OF WASHINGTON
依托单位国家：
美国
项目类别：
财政年份：
2006
资助国家：
美国
起止时间：
2006-07-15 至 2010-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7446131
关键词：
Affect Alkaline Phosphatase Animal Model Ankylosis Biological Cell membrane Cells Cementogenesis Cementum Formation Characteristics Clinical Collection Condition Defect Dental Dental Cementum Dental Pulp Dentin Dentin Formation Deposition Developed Countries Developing Countries Development Diagnosis Diphosphates Disease Enzyme-Linked Immunosorbent Assay Enzymes Equilibrium Exhibits Gene Expression Gene Proteins Genes Goals Harvest Health Human Hypercementosis Hypophosphatasia In Vitro Individual Knock-out Knockout Mice Link Membrane Glycoproteins Metabolism Microarray Analysis Minerals Modality Mus Mutant Strains Mice Mutate Mutation Natural regeneration Outcome Partner in relationship Periodontal Diseases Periodontal Ligament Periodontium Phenotype Plant Roots Plasma Cells Polymerase Chain Reaction Proteins Regulation Role Signal Transduction Site Surface Time Tissues Tooth Loss Tooth Tissue Tooth root structure Tooth structure Western Blotting Wound Healing alveolar bone base bone cell behavior extracellular inorganic phosphate insight knock-down mineralization mutant mouse model parent grant protein expression restoration success therapy design

项目摘要

DESCRIPTION (provided by applicant): For normal biological mineral deposition to proceed, a tight balance is required between the levels of extracellular inorganic phosphate (Pi and pyrophosphate (PPi) The periodontium, the collection of upportive structures of the tooth root, is especially sensitive to P\/PP\ balance, as evidenced by dramatic cementum phenotypes resulting from mutations that alter local levels of PI and PP|. A markedly increased cementum was demonstrated on the root surfaces of fully developed teeth in mice presenting mutations in either the multiple-pass transmembrane ankylosis protein (ANK) or plasma cell membrane glycoprotein-1 (PC-1); both mutations result in reduced extracellular PPi though via different mechanisms. Conversely, mice and humans with defective tissue nonspecific alkaline phosphatase (TNAP) present locally increased levels of PP|, leading to defective formation of acellular cementum, and subsequently, premature tooth loss. In contrast to these cementum phenotypes, the underlying mineralized tissue, dentin, seems to develop normally in conditions of altered P/PP|. Based on these observations, we hypothesize that periodontal ligament (PDL) cells adjacent to the tooth root cementum are more sensitive to changes in Pi levels than pulp cells adjacent to the dentin. In order to resolve the differential regulation of these two mineralized tissues, the following aims are set: (1) To determine basal differences in gene/protein expression in pulp vs. PDL cells in healthy and hypophosphatasia-diagnosed (HPP) subjects, focusing on genes/proteins associated with differentiation/mineralization and P/PPi metabolism; (2) To determine the effect that Pi treatment exerts on pulp vs. PDL cells, in vitro; and (3) To demonstrate that knocking down TNAP function in pulp and PDL cells harvested from healthy subjects results in a more dramatic change in PDL vs. pulp cell behavior, in vitro. Establishing the mechanisms by which P/PPi influence the periodontium is a critical step towards understanding the development of these tissues, with the ultimate goal of applying further insight to the design of therapies to regenerate periodontal tissues.

描述（申请人提供）：对于正常的生物学矿物质沉积，需要在细胞外无机磷酸盐水平（PI和Pyrophophate（PPI）（PPI）之间保持紧密的平衡。牙周（PPI）的牙齿的收集，牙齿根的收集，尤其是PP \平衡，尤其是PP \平衡的敏感性，该水平是pp \平衡的。 PP |在多个跨膜蛋白（ANK）或血浆糖膜蛋白1（PC-1）中，在多个跨膜蛋白（ANK）中表现出的牙齿明显增加。磷酸酶（TNAP）的PP |局部增加，导致骨质骨质的缺陷，随后牙齿丢失与这些矿物质的牙线相比，牙本质是牙本质的，似乎是在pp/pp的情况下正常出现的。与牙本质相邻的浆细胞相比，牙骨质对PI水平的变化更敏感。 PPI代谢（2）确定PI处理对PDL细胞的作用，并且（3）表明，从健康受试者中收获的TNAP功能，从而在PDL和PDL的pdl pdl pdl中造成了巨大的变化。这些组织，最终的目的是将进一步的见解应用于牙周组织再生的疗法设计。