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: 8509994
• 负责人: Sunita P Ho
• 金额: $ 12.14万
• 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/8509994
• 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(申请人提供)：这项研究的生物工程方面起源于沃尔夫定律，该定律解释了由于器官水平的机械负荷而导致的骨适应。在组织和细胞水平上，局部菌株触发机械生物学事件，并负责维持统一的功能PDL空间。然而，由于机械生物学改变的结果，在PDL-骨和PDL-牙骨质界面的应变中，均匀的PDL间隙可以向非均匀的PDL间隙移动。我们将测试细胞和组织水平的反应，这些反应可能会导致PDL空间的增加或减少，以及伴随着功能变化而产生的梯度。我们将调查：1)目的：原位骨表面和 牙齿最初是协调的，在机械载荷的作用下，会在骨-牙齿复合体内产生局部的压缩和拉伸应变。将使用与微型X射线计算机断层扫描(？-XCT)相耦合的加载设备和数字图像相关(DIC)来评估PDL间隙的变化和所产生的应变；目的2)目的2)在体内，机械生物学上活跃的压缩和拉伸部位通过基因和基质蛋白的表达促进生化变化，引起骨和牙骨质的吸收和形成，从而导致PDL间隙扩大或缩小。机械敏感基因和蛋白的表达促进了拉伸部位的矿物质形成、压缩部位的吸收，并负责维持组织和界面的完整性，这些基因和蛋白的时空结果将通过基于荧光的免疫组织化学绘制出来；目的3)目标2中确定的生化改变区域导致骨、牙骨质、PDL的结构、化学成分和力学性能发生可测量的变化(例如，拉伸应变诱导骨形成)。这一目标包括绘制PDL-骨和PDL-牙骨质界面的梯度移位。将使用最先进的高分辨率显微镜和光谱设备绘制湿PDL-骨、PDL-牙骨质、牙骨质、骨和PDL的局部结构、化学成分和机械性能的时空变化图；目标4)。就地适应功能的系统对机械载荷有不同的反应。将评估和比较新鲜收获的试验组和对照组(如目标1)第二磨牙适应复合体中的载荷-位移曲线和相关应变场。研究将使用原位负荷、XCT和DIC，与目标1相同。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荷的不完全理解。局部功能适应可能是不利的结果，由于牙根和/或骨吸收或形成导致牙齿移动范围增加或减少，导致牙周间隙变宽(牙齿松动)或变窄(强直)。当复合体受到种植体和/或牙周炎、正常或治疗性负荷(正畸支具)继而损害功能时，这些适应部位可以作为局部应力点，产生正反馈。