Ameloblast Differentiation and Amelogenesis: Next-Generation Models to Define Key Mechanisms and Factors Involved in Biological Enamel Formation

成釉细胞分化和成釉细胞:定义生物牙釉质形成涉及的关键机制和因素的下一代模型

基本信息

  • 批准号:
    10460290
  • 负责人:
  • 金额:
    $ 18.87万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2021
  • 资助国家:
    美国
  • 起止时间:
    2021-08-01 至 2023-07-31
  • 项目状态:
    已结题

项目摘要

Abstract Amelogenesis is a biological process by which highly specialized enamel organ epithelial cells called ameloblasts transport substantial amounts of calcium ions and enamel proteins into the secretory enamel matrix and manufacture a biomaterial of exceptional structural and mechanical properties: tooth enamel (Pandya and Diekwisch 2018). Recent studies have identified some of the calcium channels in dental enamel cells at the basal ameloblast aspect (Nurbaeva et al. 2015, Lacruz 2017). However, there is remarkably little agreement on the mechanisms of ion and protein trafficking at the secretory ameloblast pole and throughout the ameloblast cell body. In support of the present application we have developed three highly innovative models that will address knowledge gaps and advance our understanding of physiological and pathological amelogenesis, including (i) a conditional clathrin deletion mouse model, (ii) an ameloblast 3D bioreactor cell culture model, and (iii) a new liquid cell atomic resolution imaging technology for life in situ imaging of vesicular and extracellular enamel matrices. Establishment of a clathrin knockout model represents significant progress in the area of vesicular trafficking research and a powerful tool to study the function of coated vesicles during amelogenesis. Clathrin-coated vesicles are among the most abundant cellular vesicles, and loss of clathrin has been associated with severe and usually lethal phenotypes (Robinson 2015). Here we present exciting preliminary data demonstrating that clathrin depletion during amelogenesis resulted in altered enamel prism structure and crystal density. Our 3D bioreactor amelogenesis model marks another milestone in enamel research as it promoted the propagation of elongated amelogenin secreting cells, overcoming shortcomings of traditional 2D ameloblast cell culture technology. Third, our atomic resolution liquid chamber model facilitates unprecedented in situ imaging of vesicular contents and native enamel matrix, allowing for the identification of matrix/mineral clusters at the earliest stages of amelogenesis. In response to RFA-DE- 19-004 we have now designed a research plan to develop and optimize these model systems (UG3 phase) and to validate their physiological relevance and usefulness for understanding mechanisms of enamel development and disease during the UH3 phase.
摘要

项目成果

期刊论文数量(2)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)

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Tom Diekwisch其他文献

Tom Diekwisch的其他文献

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{{ truncateString('Tom Diekwisch', 18)}}的其他基金

Small molecule mediated restoration of periodontal homeostasis through the YAP1 pathway
小分子通过 YAP1 途径介导牙周稳态恢复
  • 批准号:
    10869312
  • 财政年份:
    2023
  • 资助金额:
    $ 18.87万
  • 项目类别:
Ameloblast Differentiation and Amelogenesis: Next-Generation Models to Define Key Mechanisms and Factors Involved in Biological Enamel Formation
成釉细胞分化和成釉细胞:定义生物牙釉质形成涉及的关键机制和因素的下一代模型
  • 批准号:
    10874800
  • 财政年份:
    2023
  • 资助金额:
    $ 18.87万
  • 项目类别:
Ameloblast Differentiation and Amelogenesis: Next-Generation Models to Define Key Mechanisms and Factors Involved in Biological Enamel Formation
成釉细胞分化和成釉细胞:定义生物牙釉质形成涉及的关键机制和因素的下一代模型
  • 批准号:
    10416108
  • 财政年份:
    2021
  • 资助金额:
    $ 18.87万
  • 项目类别:
Neurobiological control of periodontal homeostasis through microRNA, TGF-beta, and Wnt signaling
通过 microRNA、TGF-β 和 Wnt 信号传导对牙周稳态的神经生物学控制
  • 批准号:
    10112718
  • 财政年份:
    2020
  • 资助金额:
    $ 18.87万
  • 项目类别:
Neurobiological control of periodontal homeostasis through microRNA, TGF-beta, and Wnt signaling
通过 microRNA、TGF-β 和 Wnt 信号传导对牙周稳态的神经生物学控制
  • 批准号:
    9756189
  • 财政年份:
    2018
  • 资助金额:
    $ 18.87万
  • 项目类别:
Small molecule mediated restoration of periodontal homeostasis through the YAP1 pathway
小分子通过 YAP1 途径介导牙周稳态恢复
  • 批准号:
    9892878
  • 财政年份:
    2017
  • 资助金额:
    $ 18.87万
  • 项目类别:
Small molecule mediated restoration of periodontal homeostasis through the YAP1 pathway
小分子通过 YAP1 途径介导牙周稳态恢复
  • 批准号:
    9311559
  • 财政年份:
    2017
  • 资助金额:
    $ 18.87万
  • 项目类别:
Enamel Structure Sophistication throuth Amelogenin Evolution
牙釉质结构通过牙釉蛋白进化而变得复杂
  • 批准号:
    7840703
  • 财政年份:
    2009
  • 资助金额:
    $ 18.87万
  • 项目类别:
Enamel Structure Sophistication throuth Amelogenin Evolution
釉原蛋白进化带来的复杂牙釉质结构
  • 批准号:
    7880098
  • 财政年份:
    2008
  • 资助金额:
    $ 18.87万
  • 项目类别:
Enamel Structure Sophistication throuth Amelogenin Evolution
牙釉质结构通过牙釉蛋白进化而变得复杂
  • 批准号:
    7527401
  • 财政年份:
    2008
  • 资助金额:
    $ 18.87万
  • 项目类别:

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