Adaptability of Articular Cartilage to External Loading by Microscopic Imaging

描述（由申请人提供）：骨关节炎（OA）是一种主要的健康问题，影响美国2000多万人。这种疾病的主要特征是关节软骨中的承重组织逐渐退化。在OA的最早临床诊断之前，软骨内已经发生了一系列复杂的和深度依赖性的事件，在各种分子和结构水平上。由于缺乏非侵入性和分子特异性标记物来检测软骨中的早期降解事件，迄今为止，阻碍了对OA发展的基本理解，以及OA的早期诊断和干预。由于其多层次的组织，多学科的测量，询问软骨在不同的技术模式是必要的。由于其深度依赖性和异质性结构，组织对外部载荷的响应的透彻理解需要显微成像。最近，我们已经成功地成像的负载诱导的超微结构的适应性，在软骨使用高分辨率。我们使用静态加载作为一种工具，迫使组织与环境达到新的平衡，以探测软骨的内在特性和结构适应性，在成像中以深度分辨的方式。在本质上，静态加载成为一个可控的机制，以诱导额外的对比度，并提高我们的成像工作中的弱对比度。该建议的首要目标是检测病变关节软骨原位分子结构的早期变化。我们假设，在结构和分子水平上的负荷诱导的软骨变化可以通过显微镜成像方式的组合来检测，并且由于疾病或机械损伤引起的软骨退化可能会影响负荷诱导的超微结构变化，这将通过免疫组织化学成像来校准。本研究的三个具体目标将确定一组多学科参数，用于检测由于生化消化、自然病变和重复/动态负荷引起的组织对静态负荷的响应的各种变化。结合起来，该提议将超越描述和表征成像信号的水平。它旨在将这些成像技术作为疾病进展的预测因子，以及损伤和修复的监测器。骨关节炎是影响美国超过2000万人的主要健康问题，其主要特征在于关节中的承重组织关节软骨的逐渐退化。本项目旨在利用一套多学科的显微成像技术检测病变软骨原位分子结构的早期变化。

DESCRIPTION (provided by applicant): Osteoarthritis (OA) is a major health concern affecting more than 20 million people in US. The disease is predominantly characterized by a gradual degeneration of the load-bearing tissue in joint, articular cartilage. Before the earliest clinical diagnosis of OA, a series of complex and depth-dependent events at various molecular and structural levels has already taken place inside cartilage. A lack of non-invasive and molecular-specific markers to detect the early degradation events in cartilage has so far prevented a fundamental understanding of the development of OA, as well as early diagnosis of and intervention in OA. Due to its multi-level hierarchical organization, multidisciplinary measurements that interrogate cartilage at different technical modalities are warranted. Due to its depth-dependent and heterogeneous structure, a thorough understanding of tissue's response to external loading requires microscopic imaging. Recently, we have successfully imaged the load-induced ultrastructural adaptability in cartilage using at high resolution. We use static loading as a tool to force the tissue to reach a new equilibrium with the environment in order to probe cartilage's intrinsic properties and structural adaptability in a depth-resolved manner in imaging. In essence, static loading becomes a controllable mechanism to induce additional contrast and to enhance weak contrast in our imaging work. The overarching goal of this proposal is to detect the early changes in the in situ molecular architecture of diseased articular cartilage. We hypothesize that the load-induced changes in cartilage at the structural and molecular levels can be detected by a combination of microscopic imaging modalities and that the degradation in cartilage due to diseases or mechanical injury could affect load-induced ultrastructural changes, which will be calibrated by immunohistochemistry imaging. The three specific aims of this study will determine a set of multidisciplinary parameters that detects various changes in tissue's response to static loading due to biochemical digestion, natural lesion, and repetitive/dynamic loading. In combination, this proposal will go beyond the level of describing and characterizing the imaging signals. It aims to put these imaging techniques to work as the predictors of disease progression, and monitors of injury and repair. Osteoarthritis, which is a major health concern affecting more than 20 million people in US, is predominantly characterized by a gradual degeneration of the load-bearing tissue in joint, articular cartilage. This project aims to detect the early changes in the in situ molecular architecture of diseased cartilage using a set of multidisciplinary microscopic imaging techniques.