Age-Related Effect of Bone Remodeling on Bone Toughness

描述（由申请人提供）：先前的研究表明，老年骨的脆弱性增加与骨中胶原蛋白的完整性显著相关。然而，人们对其潜在机制知之甚少。本研究的目的是阐明胶原网络中与年龄相关的变化是如何诱导的，以及这些变化是否会导致骨质量的恶化。在这项拟议的研究中，我们试图研究骨重塑对胶原完整性的年龄相关影响及其与组织韧性降低的相关性。新形成的次生骨是通过骨重塑过程形成的。因此，通过研究继发性骨的变化，可以研究骨重塑对胶原完整性和骨质量的年龄依赖性影响。我们目前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诱导的；这些变化直接导致了老化骨韧性的下降。为此目的，将处理以下具体目标：目标1。假设：继发性骨的材料特性随着年龄的增长而改变。利用微机械加工装置，从60具人尸体股骨的次生骨和间质骨区制备三点弯曲试样。试样将在微力学试验装置中进行试验。骨重塑对继发性骨和间质骨组织机械完整性的年龄相关影响将被研究。目标2。为了研究继发性骨中胶原蛋白分子的年龄相关变化——假设：继发性骨中胶原蛋白分子的完整性随着年龄的变化而变化。Aim 1中机械测试的标本将被重复使用，以确定继发性骨和间质骨区域的胶原完整性。胶原变性和交联浓度将使用高效液相色谱技术测定。然后，我们将研究骨重塑对骨中胶原完整性的年龄相关影响。此外，还将探讨胶原完整性与次生骨力学行为的关系。目标3。探讨年龄相关性胶原蛋白变化与骨韧性下降的关系。假设：年龄相关性胶原蛋白变化直接导致老年骨韧性下降。胶原网络和骨骼的整体机械性能将与其他成分和结构性能一起确定为年龄的函数。结合Aims 1和Aims 2的结果，我们将研究胶原蛋白在年龄相关性骨韧性下降中的作用。这项研究将为年龄相关的骨质量恶化的潜在机制提供见解，并将促进未来对年龄和疾病相关骨折的预防和治疗的研究。

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.