Adaptability of Articular Cartilage to External Loading by Microscopic Imaging

描述(由申请人提供)：骨关节炎(OA)是一个主要的健康问题，在美国有2000多万人受到影响。该病的主要特征是关节、关节软骨中的承重组织逐渐退化。在最早的临床诊断之前，软骨内已经发生了一系列复杂的、深度相关的、不同分子和结构水平的事件。到目前为止，缺乏非侵入性和分子特异性的标记物来检测软骨的早期降解事件，阻碍了对骨关节炎发生发展的基本了解，以及对骨关节炎的早期诊断和干预。由于其多层次的等级组织，在不同的技术形态下询问软骨的多学科测量是必要的。由于其深度依赖性和异质性的结构，要彻底了解组织对外部载荷的响应需要显微成像。最近，我们成功地在高分辨率下成像了负载诱导的软骨超微结构适应性。我们使用静态载荷作为一种工具，迫使组织与环境达到新的平衡，以便在成像中以深度分辨的方式探索软骨的内在属性和结构适应性。从本质上讲，在我们的成像工作中，静态加载成为一种可控的机制来产生额外的对比度和增强弱对比度。这项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。我们假设负荷诱导的软骨在结构和分子水平上的变化可以通过显微成像手段的组合来检测，而由于疾病或机械损伤导致的软骨退化可能会影响负荷诱导的超微结构变化，这些变化将通过免疫组织化学成像来校准。这项研究的三个具体目标将确定一组多学科参数，这些参数检测由于生化消化、自然损伤和重复/动态负荷而导致的组织对静态负荷的各种变化。综合起来，这项建议将超越描述和表征成像信号的水平。它的目的是让这些成像技术作为疾病进展的预测指标，并监测损伤和修复。骨性关节炎是影响美国2000多万人的主要健康问题，其主要特征是关节、关节软骨中的承载组织逐渐退化。该项目旨在利用一套多学科的显微成像技术来检测病变软骨的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.