NIDCR Individual Predoctoral Dental Scientist Fellowship

NIDCR 个人博士前牙科科学家奖学金

基本信息

  • 批准号:
    8524386
  • 负责人:
  • 金额:
    $ 4.8万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2013
  • 资助国家:
    美国
  • 起止时间:
    2013-04-01 至 2016-03-31
  • 项目状态:
    已结题

项目摘要

DESCRIPTION (provided by applicant: The inorganic phase in bone and dentin contribute to the unique, compressive strength of these tissues. The extracellular organic phase dictates the deposition of calcium and phosphate mineral to form oriented hydroxyapatite crystals. This process is facilitated with the aid of acidic, noncollagenous proteins like dentin matrix protein 1 (DMP1). While DMP1 is known to participate as a regulatory component in the highly complex process of biomineralization in teeth and bones, its therapeutic potential and mechanism of action is not yet known. This project proposes to use two transgenic, gain-of-function models for analyzing bone and tooth biochemistry, architecture, and mechanical properties. The mouse models are designed using the osteocalcin (OC) and dentin sialophosphoprotein (DSPP) gene promoters to drive tissue-specific overexpression in bone and teeth, respectively. The overall goal of this research is to characterize how tissue- specific DMP1 overexpression alters tissue biochemistry and architecture in order to determine how increased levels of DMP1 influence their mechanical properties. The central hypothesis is that overexpression of DMP1 will modulate the extracellular architecture, increase mineral density, and thereby improve the mechanical properties of bone and dentin in transgenic mice compared to wild type. The proposed aims will determine the temporal expression of osteogenic and odontogenic genes, while also analyzing the spatio-temporal production of key proteins involved in mineralization. The architecture of bone and tooth ECM will be characterized via micro-CT analysis. Mineral density will be quantified using backscatter scanning electron microscopy. Micro and nano-scale mechanical properties will be determined using three-point bend testing and nano-indentation. These data will be statistically analyzed to determine the effect of tissue-specific DMP1 overexpression on progenitor cell differentiation and its influence on tissue mechanical properties. This knowledge would greatly assist in developing novel, tissue engineered therapies for pathological conditions of dental and craniofacial tissues.
描述(申请人提供:骨和牙本质中的无机相有助于这些组织独特的抗压强度。细胞外的有机相决定了钙和磷矿物的沉积,形成了定向的羟基磷灰石晶体。这一过程在酸性的非胶原蛋白的帮助下得以促进,如牙本质基质蛋白1 (DMP1)。虽然DMP1被认为是高度复杂的牙齿和骨骼生物矿化过程中的调节成分,但其治疗潜力和作用机制尚不清楚。这个项目建议使用两个转基因的功能增益模型来分析骨骼和牙齿的生化、结构和机械性能。小鼠模型的设计分别使用骨钙素(OC)和牙本质涎磷蛋白(DSPP)基因启动子来驱动骨骼和牙齿中组织特异性的过度表达。这项研究的总体目标是表征组织特异性的DMP1过度表达如何改变组织的生化和结构,以确定增加的DMP1水平如何影响其机械性能。核心假设是,与野生型相比,转基因小鼠过表达DMP1将调节细胞外结构,增加矿物质密度,从而改善骨和牙本质的力学性能。拟议的目标将确定成骨和成牙基因的时间表达,同时也分析参与矿化的关键蛋白质的时空生产。骨和牙齿细胞外基质的结构将通过显微CT分析来表征。矿物密度将使用背向散射扫描电子显微镜进行量化。微纳尺度的机械性能将通过三点弯曲测试和纳米压痕来确定。这些数据将被统计分析,以确定组织特异性DMP1过表达对祖细胞分化的影响及其对组织机械性能的影响。这一知识将极大地帮助开发针对牙科和颅面组织病理状况的新型组织工程疗法。

项目成果

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Joshua Padovano其他文献

Joshua Padovano的其他文献

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{{ truncateString('Joshua Padovano', 18)}}的其他基金

NIDCR Individual Predoctoral Dental Scientist Fellowship
NIDCR 个人博士前牙科科学家奖学金
  • 批准号:
    8665317
  • 财政年份:
    2013
  • 资助金额:
    $ 4.8万
  • 项目类别:

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