Adaptability of Articular Cartilage to External Loading by Microscopic Imaging

通过显微成像观察关节软骨对外部载荷的适应性

• 批准号: 7618553
• 负责人: YANG XIA
• 金额: $ 41.91万
• 依托单位: OAKLAND UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-04-30 至 2013-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7618553
• 关键词: Affect; Animals; Architecture; Biochemical; Biological; Calcified; Cartilage; Chemicals; Chemistry; Chondrocytes; Complex; Degenerative polyarthritis; Development; Digestion; Disease; Disease Progression; Early Diagnosis; Environment; Equilibrium; Event; Figs - dietary; Fourier Transform; Goals; Health; Histocytochemistry; Histology; Image; Imaging Techniques; Immunohistochemistry; In Situ; Individual; Injury; Intervention; Joints; Knowledge; Length; Lesion; Liquid substance; Magnetic Resonance Imaging; Measurable; Measurement; Mechanics; Microscopic; Modality; Modeling; Molecular; Monitor; Onset of illness; Operative Surgical Procedures; Physiological; Play; Polarization Microscopy; Population; Process; Property; Research; Resolution; Role; Series; Shock; Signal Transduction; Site; Solid; Staging; Structure; Techniques; Thick; Time; Tissues; Weight-Bearing state; Work; arthropathies; articular cartilage; bone; clinical Diagnosis; clinical practice; imaging modality; injury and repair; multidisciplinary; novel; physical property; prevent; response; tibia; tool

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.

描述（由申请人提供）：骨关节炎 (OA) 是影响美国超过 2000 万人的主要健康问题。该疾病的主要特征是关节中的承重组织、关节软骨逐渐退化。在最早的 OA 临床诊断之前，软骨内部已经在不同分子和结构水平上发生了一系列复杂且依赖于深度的事件。迄今为止，由于缺乏非侵入性和分子特异性标记物来检测软骨的早期退化事件，阻碍了对 OA 发展的基本了解，也阻碍了 OA 的早期诊断和干预。由于其多层次的分层组织，需要以不同的技术方式对软骨进行多学科测量。由于其深度依赖性和异质结构，彻底了解组织对外部载荷的反应需要显微成像。最近，我们成功地以高分辨率对软骨中负载引起的超微结构适应性进行了成像。我们使用静态加载作为工具，迫使组织与环境达到新的平衡，以便在成像中以深度分辨方式探测软骨的内在特性和结构适应性。从本质上讲，静态加载成为一种可控机制，可以在我们的成像工作中产生额外的对比度并增强弱对比度。该提案的总体目标是检测患病关节软骨原位分子结构的早期变化。我们假设，载荷引起的软骨在结构和分子水平上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引起的软骨退化可能会影响载荷引起的超微结构变化，这将被校准通过免疫组织化学成像。这项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、自然损伤和重复/动态负载而导致的组织对静态负载的反应的各种变化。结合起来，该提议将超越描述和表征成像信号的水平。它的目的是利用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，其主要特征是关节、关节软骨中的承重组织逐渐退化。该项目旨在利用一套多学科显微成像技术检测患病软骨原位分子结构的早期变化。