Adaptability of Articular Cartilage to External Loading by Microscopic Imaging

描述（由申请人提供）：骨关节炎（OA）是影响美国2000多万人的主要健康问题。这种疾病的主要特征是关节软骨中承重组织的逐渐退化。在OA最早的临床诊断之前，软骨内部已经发生了一系列复杂的、不同分子和结构水平的深度依赖事件。迄今为止，缺乏非侵入性和分子特异性标志物来检测软骨的早期降解事件，这阻碍了对OA发展的基本理解，也阻碍了OA的早期诊断和干预。由于其多层次的层次组织，多学科的测量询问软骨在不同的技术模式是必要的。由于其深度依赖和非均匀结构，彻底了解组织对外部负载的反应需要显微镜成像。最近，我们成功地利用高分辨率成像了软骨中载荷诱导的超微结构适应性。我们使用静态载荷作为工具，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测软骨的内在特性和结构适应性。在我们的成像工作中，静态加载实质上是一种可控的机制，可以诱导额外的对比度，增强弱对比度。本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。我们假设载荷诱导的软骨结构和分子水平的变化可以通过显微成像方式的组合来检测，并且由于疾病或机械损伤导致的软骨降解可能会影响载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，以检测组织对生化消化、自然损伤和重复/动态负荷引起的静态负荷反应的各种变化。综上所述，这一建议将超越描述和表征成像信号的水平。它的目标是将这些成像技术用于疾病进展的预测，以及损伤和修复的监测。骨关节炎是影响美国2000多万人的主要健康问题，其主要特征是关节软骨中承重组织的逐渐退化。本项目旨在利用一套多学科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.