Extracellular Matrix and Phosphate/Pyrophosphate Metabolism in Cementum Formation

牙骨质形成中的细胞外基质和磷酸盐/焦磷酸盐代谢

基本信息

批准号：
9303193
负责人：
Brian Lee Foster
金额：
$ 24.9万
依托单位：
OHIO STATE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2015
资助国家：
美国
起止时间：
2015-09-21 至 2019-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9303193
关键词：
Address Adult Affect Area Automobile Driving Award Back Biological Biology Cell Separation Cells Cementoblast Cementogenesis Cementum Formation Complex Crystallization Data Dental Dental Cementum Dentition Development Development Plans Diphosphates Disabled Persons Disease Environment Epithelium Extracellular Matrix Extracellular Matrix Proteins Faculty Foundations Future Gene Expression Goals Growth Histology Immunohistochemistry In Situ Hybridization In Vitro Knockout Mice Knowledge Lead Link LoxP-flanked allele Maps Mentorship Messenger RNA Metabolism Methods Minerals Molecular Mus Natural regeneration Odontogenesis Pathway interactions Periodontal Diseases Periodontium Phenotype Plant Roots Positioning Attribute Process Proteins Regulation Regulator Genes Reporting Research Research Project Grants Role Serologic tests Signal Transduction Stress Structure Testing Tissues Tooth regeneration Tooth root structure Tooth structure Training Transgenic Mice Translating Work base bone bone sialoprotein career career development design functional restoration improved in vivo inhibitor/antagonist inorganic phosphate insight inter-alpha-inhibitor laboratory experience microCT mineralization novel novel strategies osteopontin overexpression prevent programs public health relevance regenerative sensor skeletal skeletal tissue skills sodium phosphate symporter transcriptome sequencing

项目摘要

DESCRIPTION (provided by applicant): Dental cementum covering the tooth root is critical for tooth attachment, long-term stability, and function of the dentition, yet regulation of root development and cementum formation remains poorly understood, hampering efforts towards periodontal regeneration. This application is a Pathway to Independence Award proposal that aims to advance fundamental knowledge on cementum biology by addressing gaps in our current understanding of cementum formation, focusing on areas of: extracellular matrix (ECM) proteins and local phosphate/pyrophosphate regulation implicated to be central to the process of cementogenesis. We propose that a coordination of local matrix proteins and phosphate regulating factors is crucial for proper development and mineralization of cementum. This hypothesis will be tested by three specific aims: 1) To define the role of ECM protein bone sialoprotein (BSP) in cementum formation, using null and conditionally null mice and in vitro approaches; 2) To determine the function of ECM protein osteopontin (OPN) in cementum development, by evaluating OPN-pyrophosphate interactions in tooth development; 3) To establish the role of sodium- phosphate co-transporter PiT1 (SLC20A1) during cementoblast differentiation and function, by mapping its expression during periodontal development, and analyzing the phenotype in PiT1 conditional null mice, including effects on cementum regulatory factors. The applicant is a postdoctoral research fellow highly qualified to lead this research program based on his training studying cementoblasts in vitro and cementum formation in vivo, reporting on phosphate/pyrophosphate metabolism in tooth formation, driving the paradigm- shifting findings regarding pyrophosphate control of cementum formation, and discovering the necessity of ECM protein BSP for cementum mineralization. The applicant's long-term career goal is to lead a productive research program that provides significant insights into the molecular mechanisms driving tooth root formation and mineralization, and translates those insights into novel approaches for regenerating periodontal tissues and restoring function. This project is an ideal starting point for the applicant to transition to his independent research carer because it provides a framework for development of further skills necessary to accomplish the long-term goal. The proposed career development plan incorporates didactic coursework, laboratory training, and a structured mentorship plan to facilitate accomplishment of short-term goals, including development of a skill set for mineralized tissue research, establishing an independent research project, providing a pathway for a faculty position, and affording a future opportunity to build on this proposed work. The applicant's institutional environment provides strong support in areas of postdoctoral development and transition.

描述（由申请人提供）：覆盖牙齿根的牙髓对于牙齿的固定，长期稳定性和牙齿功能至关重要，但是对根发育和牙骨质形成的调节仍然很少了解，从而阻碍了牙周再生的努力。该应用是通往独立奖励提案的途径，旨在通过解决我们当前对牙骨形成的理解中的差距，重点介绍：细胞外基质（ECM）蛋白质（ECM）蛋白质和局部磷酸盐/焦油磷酸盐法规的含义是中心的。到胶结发生过程。我们建议，局部基质蛋白和磷酸盐调节因子的协调对于正确发育和矿物质至关重要。该假设将通过三个特定目的来检验：1）使用无效的和有条件的无小鼠以及体外方法来定义ECM蛋白骨唾液蛋白（BSP）在牙骨质形成中的作用； 2）通过评估牙齿发育中的OPN-磷酸盐相互作用来确定ECM蛋白骨座蛋白（OPN）在牙胶发育中的功能； 3）通过在牙周发育过程中绘制其表达，并分析PIT1条件无效小鼠的表型，包括磷酸钠共转运蛋白PIT1（SLC20A1）的作用，包括对胶质调节性因子的效力。申请人是一项博士后研究研究员，基于他的培训，基于他的培训，该研究基于他的培训，该研究研究了体内的胶结细胞和正水泥细胞的研究，报告了牙齿形成中磷酸盐/焦磷酸盐代谢的报道，推动了范式促进范式 - 促进范式的发现，这些发现涉及有关水泥磷酸盐的形成的发现。，并发现ECM蛋白BSP进行牙骨质矿化的必要性。申请人的长期职业目标是领导一项生产研究计划，该计划为推动牙齿根形成和矿化的分子机制提供了重大见解，并将这些见解转化为用于再生牙周组织和恢复功能的新方法。该项目是申请人过渡到其独立研究护理人员的理想起点，因为它为开发实现长期目标所需的进一步技能提供了框架。拟议的职业发展计划纳入了教学课程，实验室培训和结构化指导计划，以促进短期目标的实现，包括开发用于矿化组织研究的技能，建立独立的研究项目，为教师职位提供途径，并提供未来的机会，以这项拟议的工作为基础。申请人的机构环境为博士后发展和过渡领域提供了强有力的支持。

项目成果

期刊论文数量（6）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Global proteome profiling of dental cementum under experimentally-induced apposition.

实验诱导并置下牙骨质的整体蛋白质组分析。

DOI：
10.1016/j.jprot.2016.03.036
发表时间：
2016
期刊：
Journal of proteomics
影响因子：
3.3
作者：
Salmon,CristianeR;Giorgetti,AnaPaulaO;PaesLeme,AdrianaFranco;Domingues,RomêniaR;Sallum,EnilsonAntonio;Alves,MarceloC;Kolli,TamaraN;Foster,BrianL;NocitiJr,FranciscoH
通讯作者：
NocitiJr,FranciscoH

The Cementocyte-An Osteocyte Relative?

DOI：
10.1177/0022034516641898
发表时间：
2016-07-01
期刊：
JOURNAL OF DENTAL RESEARCH
影响因子：
7.6
作者：
Zhao, N.;Foster, B. L.;Bonewald, L. F.
通讯作者：
Bonewald, L. F.

Standardized assessment of bone micromorphometry around teeth following orthodontic tooth movement : A µCT split-mouth study in mice.

DOI：
10.1007/s00056-021-00336-9
发表时间：
2022-11
期刊：
JOURNAL OF OROFACIAL ORTHOPEDICS-FORTSCHRITTE DER KIEFERORTHOPADIE
影响因子：
1.7
作者：
Trelenberg-Stoll, Viktoria;Wolf, Michael;Busch, Caroline;Drescher, Dieter;Becker, Kathrin
通讯作者：
Becker, Kathrin

On the discovery of cementum.