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

牙釉质缺陷和牙齿缺失影响着我们一半以上的人口，导致巨大的痛苦和经济成本。如果对负责产生牙釉质的细胞有更多的了解，那么许多牙釉质缺陷可能会得到预防，替换的牙齿也会变得更加逼真。一个特别的问题是我们缺乏对釉质形成细胞如何避免钙过量的理解，钙过量会导致细胞毒性。本研究以大鼠牙胚为实验模型，利用最新的细胞生物学和生物化学技术，探讨釉细胞钙离子转运的机制。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。我们将测试一个新的理论，已经从我们的调查，使用药物和基因沉默技术来干扰细胞机制，现在被认为是至关重要的钙运输。通过为这种新机制提供强有力的生理学证据，我们的预期结果将确定药物和营养可能靶向的特定蛋白质，并提供有关膳食氟化物和咖啡因如何影响牙釉质质量的重要信息。这些发现将改变人们对如何预防牙釉质缺陷的思考，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天然替代牙齿。

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.