Biomechanical and Molecular Mechanisms in Alveolar Bone Development

描述（由申请人提供）：本研究的长期目标是确定牙齿负荷如何指导牙根槽骨的发育，因为牙齿萌出功能。首席研究员Tracy Popowics博士是华盛顿大学牙科学院的助理教授，该研究将在那里进行。这所大学提供了一个良好的研究环境，包括医学和牙科学校，在联邦研究支持方面一直位居全国前列。Popowics博士的研究生涯将通过以下方式发展：1）将她的研究范围扩大到矿化组织的发育和功能，包括骨骼; 2）获得进行分子生物学研究的必要技能。拟议的研究测试的假设，RANKL，RANK和OPG分子的表达在发育中的牙槽骨调节牙槽骨从牙齿萌出过程中的建模到咬合功能过程中的重塑的过渡，以及萌出后的牙齿负荷提供了松质牙槽骨中RANKL的成骨细胞表达的变化的机制。在具体目标1中，将测量不同发育阶段牙槽骨的结构和生物力学特性。这些数据将检验这样的假设，即在整个发育过程中，骨的质量、刚度和强度增加，但骨性牙齿支撑的各向异性仅随着牙齿载荷而增加。具体目标2使用分子方法定位RANKL、RANK、OPG和CSF-1在牙周组织中的表达，并检验机械负荷增加RANKL的成骨细胞表达，从而促进松质牙槽骨中的破骨细胞生成的假设。在特定目标3中，将通过从萌出的M1中移除牙齿载荷来测试牙齿载荷对牙槽骨生长和重塑的影响。将在对照骨与这些实验条件下比较牙槽骨沉积和转换以及RANKL、RANK、OPG表达。总之，这些研究将提供关于牙齿负荷如何改变新萌出牙齿的牙槽骨和促进适应性牙齿支持的基本新信息。

DESCRIPTION (provided by applicant): The long-term goal of this research is the identification of how tooth loading directs development of radicular alveolar bone, as the tooth erupts into function. The principal investigator, Dr. Tracy Popowics, is an assistant professor at the University of Washington School of Dentistry where the research will be conducted. The university offers an excellent environment for research, including both medical and dental schools that consistently rank among the top in the nation in terms of federal research support. The proposed research will develop Dr. Popowics's research career by 1) expanding the scope of her investigations into the development and function of mineralized tissue to include bone, and 2) acquiring the necessary skills to pursue molecular biology research. The proposed research tests the hypotheses that the expression of RANKL, RANK, and OPG molecules within the developing alveolar bone regulates the transition in alveolar bone from modeling during tooth eruption to remodeling during occlusal function, and that post-eruptive tooth loads provide the mechanism for shifts in osteoblast expression of RANKL in cancellous alveolar bone. In Specific Aim 1, the structural and biomechanical properties of alveolar bone will be measured at different developmental stages. These data will test the hypothesis that bone increases in mass, stiffness and strength throughout development, but that osseous tooth support increases in anisotropy only with tooth loading. Specific Aim 2 uses molecular methodologies to localize the expression of RANKL, RANK, OPG, and CSF-1 in periodontal tissues, and test the hypothesis that mechanical loads increase the osteoblast expression of RANKL, thus promoting osteoclastogenesis in cancellous alveolar bone. In Specific Aim 3, the effects of tooth loading on the growth and remodeling of alveolar bone will be tested through removing tooth loads from erupting M1's. Alveolar bone apposition and turnover and RANKL, RANK, OPG expression will be compared in control bone vs. these experimental conditions. Taken together, these studies will provide fundamental new information about how tooth loading modifies alveolar bone in newly erupted teeth and promotes adaptive tooth support.