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当牙齿进入功能时，牙齿负荷如何指导根状牙槽骨的发育。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。这所大学为研究提供了良好的环境，包括医学和牙科学院，在联邦研究支持方面一直名列全国前茅。拟议的研究将通过以下方式发展Popowics博士的研究事业：1)扩大她对矿化组织的发育和功能的研究范围，包括骨骼；2)获得从事分子生物学研究所需的技能。本研究验证了以下假设：发育中的牙槽骨中RANKL、RANK和OPG分子的表达调节了牙槽骨从萌牙期间的模塑到咬合功能期间的重塑的转变，而萌牙后的牙齿负荷为松质牙槽骨中RANKL成骨细胞表达的转变提供了机制。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。这些数据将验证骨骼在整个发育过程中质量、刚度和强度增加的假设，但骨性牙齿支持的各向异性仅随着牙齿负载的增加而增加。Specific Aim 2利用分子方法定位了RANKL、RANK、OPG和CSF-1在牙周组织中的表达，并验证了机械负荷增加RANKL成骨细胞表达从而促进松质牙槽骨破骨细胞发生的假设。在Specific Aim 3中，我们将通过去除萌牙M1的牙齿负荷来测试牙齿负荷对牙槽骨生长和重塑的影响。将对照骨与这些实验条件下的牙槽骨的移位和转换以及RANKL、RANK、OPG的表达进行比较。综上所述，这些研究将提供关于牙齿负荷如何改变新出牙齿的牙槽骨并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.