AGE-RELATED CHANGES IN DAMAGE ACCUMULATION IN CORTICAL AND SUBCHONDRAL BONE

软硬组织力学性质的有害变化 是关节炎和肌肉骨骼疾病的核心。中心到 这些力学性能的变化是基质的降解或损坏。 损伤被定义为组织结构的永久性变化(例如，裂缝) 这会导致材料性能退化。超负荷，创伤，和 重复负荷导致关节软骨退行性改变和 骨性关节炎患者的软骨下骨。据信， 软骨下骨硬化症可能在软骨中起重要作用 退化。然而，促进骨形成的刺激并不是 很好理解。基于先前在皮质骨方面的工作，该工作表明 我们假设，这种损害是对重塑过程的刺激 与骨关节炎相关的硬化性改变代表着一种 修复对改变的伤害累积机制的反应 软骨下骨。在目前的研究中，我们建议测试 皮质和软骨下骨中的蓄积机制随着 年龄。我们将以分层的方式解决这些问题，方法是 组织(毫米尺度)和基质(微米尺度)结构的测试 级别。具体地说，我们建议完成以下工作： 1.确定组织水平的损伤累积机制是否在 皮质骨随着年龄的增长而发生显著变化。 2.研制了一套能够实现微机械性能测试的系统 量化大脑皮层和大脑皮层基质水平损伤机制的变化 软骨下骨。 这项提议将提供机会发展相关的数据， 对疾病过程的研究以及开发 解决这些矩阵征费所需的微观机械测试工具 软骨下骨的改变。

Deleterious changes in the mechanical properties of soft and hard tissues are at the heart of arthritis and musculoskeletal disease. Central to these changes in mechanical properties is matrix degradation or damage. Damage is defined as a permanent change in tissue structure (e.g. crack) that results in material property degradation. Overload, trauma, and repetitive loading lead to degenerative changes in the joint cartilage and underlying subchondral bone in osteoarthritis. It is believed that sclerosis of the subchondral bone may play an important role in cartilage degradation. However, the stimulus for the increased bone formation is not well understood. Based on previous work in cortical bone which suggested that damage acts as a stimulus for the remodeling process, we postulate that the sclerotic changes associated with osteoarthritis represent a repair response to altered damage accumulation mechanisms in the subchondral bone. In the current study, we propose to test whether damage accumulation mechanisms in cortical and subchondral bone are altered with age. We will address these issues in a hierarchical manner by conducting tests at both the tissue (mm scale) and matrix (micron scale) structural levels. Specifically, we propose to accomplish the following: 1. To determine whether tissue-level damage accumulation mechanisms in cortical bone are significantly altered with age. 2. To develop a micro-mechanical testing system which is capable of quantifying alterations in matrix-level damage mechanisms in cortical and subchondral bone. This proposal will provide the opportunity to develop relevant data which is fundamental to studies of the disease process as well as to develop the micro-level mechanical testing tools needed to address these matrix levy changes in subchondral bone.