Load-mediated Adaptation of the Bone-PDL-Tooth Complex in Vertebrates

脊椎动物中骨-PDL-牙齿复合物的负载介导的适应

• 批准号: 8596810
• 负责人: Sunita P Ho
• 金额: $ 48.66万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-02-09 至 2017-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8596810
• 关键词: Animal Model; Ankylosis; Biochemical; Biological; Biomechanics; Biomedical Engineering; Bone Resorption; Bone Surface; Braces-Orthopedic appliances; Cells; Chemical Structure; Clinical; Complex; Control Groups; Coupled; Cytoskeleton; Data; Dental Cementum; Devices; Diet; Equipment; Evaluation; Event; Feedback; Fibronectins; Fluorescence; Gene Expression; Gene Proteins; Guidelines; Harvest; Health; Human; Image; Immunohistochemistry; Implant; In Situ; Injury; Investigation; Laws; Ligaments; Mandible; Maps; Measurable; Mechanics; Mediating; Microscopy; Minerals; Modeling; Molecular Conformation; Motion; Musculoskeletal System; Organ; Orthodontic; Orthopedics; Osteogenesis; Outcome; Pattern; Periodontitis; Plant Roots; Property; Proteins; Rattus; Research; Resolution; Scheme; Site; Skeletal bone; Soft Diet; Specimen; Spectrum Analysis; Stress; System; TNFSF11 gene; Tendon structure; Testing; Therapeutic; Time; Tissues; Tooth structure; Translational Research; Vertebrates; X-Ray Computed Tomography; alveolar bone; asporin; base; biglycan; bone; digital imaging; effective therapy; feeding; in vivo; in vivo Model; insight; protein expression; response; skeletal; spatiotemporal; theories; vector; virtual

DESCRIPTION (provided by applicant): The bioengineering aspect of this research originates from Wolff's law which explains bone adaptation due to mechanical loads at an organ-level. At a tissue- and a cell-level, local strains trigger mechanobiological events and are responsible for maintaining a uniform functional PDL-space. However, a uniform PDL-space can shift toward a nonuniform PDL-space due to aberrations in strains at the PDL-bone and PDL-cementum interfaces as a result of altered mechanobiology. We wil test cell- and tissue-level responses that could cause an increase or decrease in PDL-space and the accompanying gradients that result from a change in function. We will investigate: Aim 1) that in situ the surfaces of bone and tooth are originally conforming and with application of mechanical load can induce localized compressive and tensile strains within the bone-tooth complex. Changes in PDL-space and resulting strains will be evaluated using a loading device coupled to a Micro X-ray computed tomography (¿-XCT) followed by digital image correlation (DIC) of virtual sections taken at no load and loaded conditions; Aim 2) that in vivo the mechanobiologically active compression and tension sites promote biochemical changes through expression of genes and matrix proteins, causing resorption and formation of bone and cementum resulting in a widened or a narrowed PDL-space. The spatiotemporal outcomes of mechanosensitive genes and protein expressions promoting mineral formation at the tension sites, resorption at the compression sites, and responsible for maintaining tissue and interface integrity will be mapped by using fluorescence based immunohistochemistry; Aim 3) that biochemically altered regions identified in Aim 2 cause measurable changes in structure, chemical composition and mechanical properties of bone, cementum, PDL (e.g. tensile strains induce bone formation). This aim includes mapping the shifts in gradients of the PDL-bone and PDL-cementum interfaces. Spatiotemporal changes in local structure, chemical composition and mechanical properties of wet PDL-bone, PDL-cementum, cementum, bone, and PDL using state-of-the-art high resolution microscopy and spectroscopy equipment will be mapped; Aim 4). the functionally adapted systems in situ have an altered response to mechanical loads. Load-displacement curves and correlating strains fields in adapted complexes of 2nd molar from freshly harvested experimental groups and controls (as in Aim 1) will be evaluated and compared. Studies will use in situ loading, ¿-XCT, and DIC as in Aim 1. HEALTH RELEVANCE: The proposed translational research is based on our incomplete understanding of how PDL-space adapts to functional loads. Local functional adaptations can be unfavorable outcomes with an increased or a decreased range of tooth motion due to root and/or bone resorption or formation resulting in a widened (tooth loosening) or narrowed PDL-space (ankylosis). Such adapted sites could act as the local stress points inducing positive feedback when the complex is subjected to implants and/or periodontitis, normal or therapeutic loads (orthodontic braces) subsequently impairing function.

描述（由适用提供）：这项研究的生物工程方面源自沃尔夫定律，该定律解释了由于器官级别的机械载荷引起的骨骼适应。在组织和细胞水平的局部应变触发机械事件，并负责维持均匀的功能性PDL空间。然而，由于机械生物学的改变，均匀的PDL空间可以朝着非均匀的PDL空间转移，因为PDL骨和PDL-scementum接口处的菌株差异。我们将测试细胞和组织级的响应，可能导致PDL空间增加或减少，以及功能变化导致的参与梯度。我们将调查：目标1）原位骨骼和 牙齿最初是符合的，并且使用机械载荷可以在骨齿配合物中诱导局部压缩和拉伸菌株。 PDL空间和所得菌株的变化将使用与微型X射线计算机断层扫描（�-XCT）结合的加载设备进行评估，然后是在无负载和负载条件下进行的虚拟部分的数字图像相关（DIC）；目标2）在体内机械主动的压缩和张力位点通过基因和基质蛋白的表达促进生化变化，从而导致骨和骨质的分辨率和形成，从而导致PDL空间扩大或狭窄。机械基因和蛋白质表达的空间时间结局，促进张力部位的矿物质形成，压缩部位的分辨率以及负责维持组织和界面完整性的矿物质形成，将使用基于荧光的免疫组织化学来映射。目的3）在AIM 2中鉴定出的生化改变区域，导致骨，骨质，PDL的结构，化学成分和机械性能的可测量变化（例如，拉伸菌株诱导骨形成）。此目的包括映射PDL骨和PDL-centsum界面的梯度的变化。使用最先进的高分辨率显微镜和光谱设备的湿PDL骨，PDL颈部，骨质，骨骼，骨骼和PDL的局部结构，化学组成和机械性能的时空变化；目标4）。功能适中的系统原位对机械载荷的响应发生了改变。将评估和比较，将评估和比较，从新鲜收获的实验组和对照组（如AIM 1）中，将评估并比较，将评估并比较，将评估和比较，从新鲜收获的实验组和对照组中的第二个磨牙的适应络合物中的载荷解散曲线和相关的应变场相关。研究将使用原位负载，� -xct和DIC与AIM 1。健康相关性：拟议的翻译研究基于我们对PDL空间如何适应功能负载的不完全理解。局部功能适应可能是不利的结果，由于根和/或骨骼分辨率或形成导致牙齿运动范围增加或减少，导致PDL空间变宽（牙齿松动）或狭窄的PDL空间（Ankyloasis）。当复合物遭受焦虑和/或牙周炎，正常或治疗载荷（正畸牙套）随后损害功能时，这种适应性位点可以充当局部应力点，从而引起正面反馈。