Biomechanical and Molecular Mechanisms in Alveolar Bone Development

描述（由申请人提供）：这项研究的长期目标是确定当牙齿萌出并发挥功能时，牙齿负荷如何指导根基牙槽骨的发育。首席研究员 Tracy Popowics 博士是华盛顿大学牙科学院的助理教授，该研究将在该学院进行。该大学提供了良好的研究环境，包括在联邦研究支持方面始终位居全国前列的医学院和牙科学院。拟议的研究将通过以下方式发展 Popowics 博士的研究生涯：1）扩大她对矿化组织发育和功能的研究范围，将骨骼包括在内；2）获得进行分子生物学研究所需的技能。该研究测试了以下假设：发育中的牙槽骨内 RANKL、RANK 和 OPG 分子的表达调节牙槽骨从牙齿萌出期间的建模到咬合功能期间重塑的转变，并且萌发后的牙齿负荷为松质牙槽骨中 RANKL 成骨细胞表达的变化提供了机制。在具体目标 1 中，将在不同发育阶段测量牙槽骨的结构和生物力学特性。这些数据将检验以下假设：骨骼在整个发育过程中质量、刚度和强度都会增加，但骨质牙齿支撑的各向异性仅随着牙齿负荷的增加而增加。具体目标 2 使用分子方法定位牙周组织中 RANKL、RANK、OPG 和 CSF-1 的表达，并检验机械负荷增加 RANKL 成骨细胞表达，从而促进松质牙槽骨中破骨细胞生成的假设。在具体目标 3 中，将通过消除 M1 萌出时的牙齿负荷来测试牙齿负荷对牙槽骨生长和重塑的影响。将比较对照骨与这些实验条件下的牙槽骨沉积和更新以及 RANKL、RANK、OPG 表达。总而言之，这些研究将提供有关牙齿负荷如何改变新萌出的牙齿中的牙槽骨并促进适应性牙齿支撑的基本新信息。

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.