CEMENTOGENESIS--ROLE OF HERTWIGS EPITHELIAL ROOT SHEATH

牙周病和牙齿植入的主要问题之一是 牙周组织如牙骨质、牙周 韧带和牙槽骨。积累了大量的知识， 近年来与骨再生有关，然而，我们对 牙骨质和牙周膜的再生仍不清楚。是 这项研究的长期目标是了解细胞和 牙骨质形成和牙根附着的分子机制 对健康牙周组织中牙周膜的影响。在本申请中， 我们专注于牙骨质的形成，特别是Hertwig的作用， 上皮根鞘（HERS）细胞在这一过程中。虽然角色 HERS细胞在牙骨质形成中的作用被广泛接受， 这些细胞的功能和命运仍然存在争议。我们建议 测试HERS细胞合成和分泌釉质的假设， 形成中间和脱细胞牙骨质的相关蛋白质， 这些细胞经历上皮-间充质转化， 成牙骨质细胞在牙根表面形成细胞牙骨质。这个项目 将利用永生鼠来源的HERS细胞系 建立在我们的实验室。实验的目的是首先 确定HERS细胞表达的釉质相关蛋白是否 是体外牙骨质形成所必需的。监管机制导致 上皮间质转化和牙骨质的性质 将研究形成的细胞外基质。最后我们将 检查使用HERS细胞在体外确定的事件是否也发生 使用小鼠动物模型放置在体内。在此生成的数据 这项研究将提供有关根系形成的宝贵信息， 将有助于阐明HERS在牙骨质形成中的作用， 如何提高牙齿脱落的诊断，治疗和预后， 衰老或牙周病。

One of the major problems in periodontal disease and tooth implants is the regeneration of periodontal tissues such as cementum, periodontal ligament and alveolar bone. Considerable knowledge as accumulated in recent years related to bone regeneration, however, our understanding of cementum and periodontal ligament regeneration is still obscure. It is the long term objective of this study to understand the cellular and molecular mechanisms underlying cementum formation and root attachment to periodontal ligament in the health periodontium. In this application, we focus on cementum formation and in particular the role of Hertwig's Epithelial Root Sheath (HERS) cells in this process. Although the role of HERS cells in cementum formation is widely accepted, the precise function and fate of these cells remains controversial. We propose to test the hypothesis that HERS cells synthesize and secrete enamel- related proteins which form intermediate and acellular cementum and then these cells undergo epithelial-mesenchymal transformation to become cementoblasts to form cellular cementum upon root surfaces. This project will take advantage of an Immortomouse-derived HERS cell line established in our laboratory. Experiments are designed to first determine if the enamel-related proteins expressed by the HERS cells are necessary for cementogenesis in vitro. The regulatory mechanisms leading to epithelial-mesenchymal transformation and the nature of the cementum extracellular matrix formed will be investigated. Finally, we will examine if the events determined using the HERS cells in vitro also take place in vivo using the mouse animal model. The data generated in this study will provide valuable information related to root formation and will help to clarify the role of HERS in cementum formation and possible ways to improve the diagnosis, treatment and prognosis of tooth loss due to aging or periodontal diseases.