Age-Related Effect of Bone Remodeling on Bone Toughness

骨重塑对骨韧性的年龄相关影响

• 批准号: 7174140
• 负责人: Xiaodu Wang
• 金额: $ 1.54万
• 依托单位: UNIVERSITY OF TEXAS SAN ANTONIO
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-05-15 至 2008-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7174140
• 关键词: bone density; bone fracture; collagen; disease /disorder onset; femur; high performance liquid chromatography; human tissue; mechanical stress; osteoporosis; pathologic bone resorption; pathologic process; postmortem

DESCRIPTION (provided by applicant): Previous studies have demonstrated that the increased fragility of aged bone correlates significantly with the integrity of collagen in bone. However, the underlying mechanism is poorly understood. The objective of this study is to elucidate how age-related changes are induced in the collagen network and whether such changes lead to the deterioration in bone quality. In this proposed study, we attempt to investigate the age-related effect of bone remodeling on the integrity of collagen and its correlation with the reduced toughness of the tissue. It has been known that newly formed secondary osteons are formed through bone remodeling process. Thus, by studying changes in the secondary osteons, one can examine the age-dependent effect of bone remodeling on the collagen integrity and the quality of bone. Our hypothesis of the present proposal is that age-dependent changes in collagen molecules are induced through bone remodeling process; and such changes directly contribute to the decreased toughness of aged bone. To this end, the following Specific Aims will be addressed: Aim 1. To examine age-related changes in material properties of the secondary osteons- Hypothesis: Material properties of secondary osteons change with increasing age. Three-point bending test specimens will be prepared from the secondary osteons and interstitial bone regions of sixty human cadaveric femurs using a micromachining device. The specimens will be tested in a micro mechanical testing device. The age-related effect of bone remodeling on the mechanical integrity of secondary osteons and interstitial bone tissues will be investigated. Aim 2. To examine age-related changes in collagen molecules within the secondary osteons-Hvpothesis: The integrity of collagen molecules in secondary osteons changes with age. The specimens mechanically tested in Aim 1 will be reused to determine the collagen integrity in the secondary osteons and interstitial bone regions. Collagen denaturation and crosslinks concentrations will be determined using high performance liquid chromatography techniques. Then, the age-related effect of bone remodeling on the integrity of collagen in bone will be investigated. In addition, the correlation of collagen integrity and mechanical behavior of secondary osteons will be explored. Aim 3. To explore the correlation of age-related changes in collagen with the decreased toughness of bone-Hypothesis: Age-related changes in collagen directly contribute to the decreased toughness of aged bone. Bulk mechanical properties of the collagen network and bone will be determined as a function of age in conjunction with other compositional and structural properties. Combining the results of Aims 1 and 2, the role of collagen in the age-related decrease in bone toughness will be investigated. This study will provide insights in the underlying mechanism of age-related deterioration in bone quality and will facilitate future studies in the prevention and treatment of age and disease-related bone fractures.

描述（由申请人提供）：先前的研究表明，老化骨骼的脆性增加与骨骼中胶原蛋白的完整性显着相关。然而，人们对其基本机制知之甚少。本研究的目的是阐明胶原蛋白网络如何引起与年龄相关的变化，以及这些变化是否会导致骨质量恶化。在这项拟议的研究中，我们试图研究骨重塑对胶原蛋白完整性的年龄相关影响及其与组织韧性降低的相关性。已知新形成的次级骨是通过骨重塑过程形成的。因此，通过研究次级骨的变化，可以检查骨重塑对胶原完整性和骨质量的年龄依赖性影响。我们对当前提案的假设是，胶原蛋白分子的年龄依赖性变化是通过骨重塑过程引起的；而这种变化直接导致老化骨骼的韧性下降。为此，将解决以下具体目标： 目标 1. 检查次级骨材料特性与年龄相关的变化 - 假设：次级骨材料特性随着年龄的增加而变化。使用微加工装置从 60 具人体股骨的次生骨和间质骨区域制备三点弯曲测试样本。样本将在微型机械测试装置中进行测试。将研究骨重塑对次生骨和间质骨组织机械完整性的年龄相关影响。目标 2. 检查次级骨内胶原蛋白分子与年龄相关的变化-假设：次级骨内胶原蛋白分子的完整性随年龄而变化。目标 1 中经过机械测试的样本将被重复使用，以确定次级骨和间质骨区域中的胶原完整性。胶原变性和交联浓度将使用高效液相色谱技术测定。然后，将研究骨重塑对骨中胶原蛋白完整性的年龄相关影响。此外，还将探讨胶原完整性与次级骨机械行为的相关性。目的3.探讨胶原蛋白与年龄相关的变化与骨骼韧性下降的相关性-假设：胶原蛋白与年龄相关的变化直接导致老化骨骼韧性的下降。胶原网络和骨的整体机械特性将根据年龄以及其他成分和结构特性来确定。结合目标 1 和 2 的结果，将研究胶原蛋白在与年龄相关的骨韧性下降中的作用。这项研究将深入了解与年龄相关的骨质量恶化的潜在机制，并将促进未来预防和治疗与年龄和疾病相关的骨折的研究。