Active transport of calcium across dental enamel cells - testing a new paradigm

钙跨牙釉质细胞的主动运输——测试新范例

• 批准号: nhmrc : 350438
• 负责人: Prof Michael Hubbard
• 金额: $ 17.2万
• 依托单位: The University of Melbourne
• 依托单位国家: 澳大利亚
• 项目类别: NHMRC Project Grants
• 财政年份: 2005
• 资助国家: 澳大利亚
• 起止时间: 2005-01-01 至 2007-12-31
• 项目状态: 已结题
• 来源: https://researchdata.edu.au/active-transport-calcium-new-paradigm/82550
• 关键词: Active; transport; calcium; across; dental

Dental enamel defects and tooth loss affect over half our population, resulting in substantial suffering and economic costs. It is likely that many enamel defects could be prevented, and replacement teeth made more lifelike, if more was known about the cells responsible for producing enamel. A particular problem is our lack of understanding about how enamel-forming cells avoid overdosing on calcium, which can lead to cellular toxicity. The overall aim of this research is to use the latest cell biology and biochemical techniques to elucidate the mechanisms of calcium handling in enamel cells, with developing teeth from rat as the experimental model. Our focus is on calcium transport mechanisms, a field where past theories were overturned by our recent findings with gene-knockout animals. We will test a new theory that has arisen from our investigations, using drugs and gene-silencing techniques to interfere with the cellular machinery now thought to be crucial for transporting calcium. By providing strong physiological evidence for this new mechanism, our expected results will define specific proteins that might be targeted by drugs and nutrition, and provide important information about how dietary fluoride and caffeine affect enamel quality. These findings would change thinking about how enamel defects can be prevented and provide a solid foundation to the exciting new field of dental bioengineering, whose goal is to coax stem cells to make natural replacement teeth.

牙釉质缺损和牙齿脱落影响着超过一半的人口，造成了巨大的痛苦和经济损失。如果对产生牙釉质的细胞有更多的了解，很可能可以预防许多牙釉质缺陷，并使替代牙齿更逼真。一个特别的问题是我们缺乏对形成珐琅质的细胞如何避免过量的钙的理解，这可能导致细胞毒性。本研究的总体目的是利用最新的细胞生物学和生物化学技术来阐明钙在牙釉质细胞中的处理机制，并以发育中的大鼠牙齿为实验模型。我们的重点是钙转运机制，过去的理论被我们最近在基因敲除动物身上的发现所推翻。我们将测试从我们的研究中产生的一个新理论，使用药物和基因沉默技术来干扰现在被认为对钙运输至关重要的细胞机制。通过为这一新机制提供强有力的生理证据，我们预期的结果将确定可能被药物和营养靶向的特定蛋白质，并为膳食氟化物和咖啡因如何影响牙釉质提供重要信息。这些发现将改变人们对如何预防牙釉质缺陷的看法，并为令人兴奋的牙科生物工程新领域提供坚实的基础，该领域的目标是诱导干细胞制造自然替代牙齿。