Biomechanical and Molecular Mechanisms in Alveolar Bone Development

牙槽骨发育的生物力学和分子机制

• 批准号: 7260519
• 负责人: TRACY E POPOWICS
• 金额: $ 13.5万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-09-06 至 2009-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7260519
• 关键词: Adopted; Affect; Alveolar; Alveolus; Anisotropy; Biomechanics; Bone Development; Bone remodeling; Characteristics; Clinical Management; Condition; Data; Dental Schools; Deposition; Development; Environment; Family suidae; Goals; Growth; Human; Implant; Investigation; Ligands; Localized; Macrophage Colony-Stimulating Factor; Measures; Mechanics; Medical; Methodology; Modeling; Molecular; Molecular Biology; Numbers; Osteoblasts; Osteoclasts; Periodontium; Play; Principal Investigator; Property; Relative (related person); Research; Research Support; Role; School Dentistry; Staging; Structure; Sus scrofa; TNFSF11 gene; Testing; Tissue Engineering; Tissues; Tooth eruption; Tooth root structure; Tooth structure; Tumor necrosis factor receptor 11b; Universities; Washington; Work; alveolar bone; bone; career; craniofacial; expectation; interdisciplinary approach; osteoclastogenesis; prevent; professor; receptor; receptor expression; research study; response; skills

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.

描述(申请人提供)：这项研究的长期目标是确定牙齿负荷如何引导牙根牙槽骨的发育，因为牙齿萌发进入功能状态。首席研究员特蕾西·波波维奇博士是华盛顿大学牙学院的助理教授，这项研究将在那里进行。该大学提供了良好的研究环境，包括医学和牙科学校，这些学校在联邦研究支持方面一直位居全国前列。这项拟议的研究将通过1)扩大她对矿化组织的发育和功能的研究范围以包括骨骼，以及2)获得从事分子生物学研究的必要技能，从而发展Popowics博士的研究生涯。本研究验证了以下假设：RANKL、RANK和OPG分子在牙槽骨发育过程中的表达调节牙槽骨从萌出时的建模向咬合功能时的改建的转变，以及萌出后的牙齿负荷提供了松质牙槽骨中成骨细胞RANKL表达变化的机制。在具体目标1中，将测量不同发育阶段的牙槽骨的结构和生物力学特性。这些数据将检验这一假设，即骨骼在整个发育过程中质量、硬度和强度都会增加，但骨性牙齿的支持只有在牙齿负荷的情况下才会增加各向异性。特异性目的2利用分子生物学方法定位RANKL、RANK、OPG和CSF-1在牙周组织中的表达，验证机械负荷增加成骨细胞RANKL表达，从而促进松质牙槽骨破骨形成的假说。在特定目的3中，通过去除M1‘S萌出时的牙齿载荷，检测牙齿载荷对牙槽骨生长和改建的影响，并比较对照骨和这些实验条件下牙槽骨的对位和转换以及RANK1、RANK、OPG的表达。综上所述，这些研究将提供有关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。