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: 7793470
• 负责人: YANG XIA
• 金额: $ 44.67万
• 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/7793470
• 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; 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; operation; 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软骨关节中承重组织的逐渐变性。在对OA的最早临床诊断之前，在软骨内已经发生了一系列复杂和深度依赖性事件。到目前为止，缺乏检测软骨早期降解事件的非侵入性和分子特异性标记，这阻止了对OA发展的基本了解，以及对OA的早期诊断和干预。由于其多级分层组织，有必要以不同技术方式询问软骨的多学科测量值。由于其深度依赖性和异质结构，对组织对外部载荷的反应的透彻理解需要微观成像。最近，我们使用高分辨率成功地对软骨中负载诱导的超微结构适应性进行了成像。我们使用静态载荷作为一种工具，迫使组织达到与环境的新平衡，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。从本质上讲，静态负载成为诱导更多对比度并增强成像工作中弱对比度的可控机制。该提案的总体目标是检测患病关节软骨的原位分子结构的早期变化。我们假设可以通过微观成像方式的组合检测到结构和分子水平的软骨的负载诱导的软骨变化，并且由于疾病或机械损伤而导致的软骨导致的软骨降解可能会影响负载诱导的超微结构变化，这将通过免疫组织化学化学成像来校准。这项研究的三个特定目的将确定一组多学科参数，这些参数检测到组织对生化消化，自然病变和重复/动态载荷引起的组织对静态负荷的反应的各种变化。结合起来，该建议将超出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指标，并监测受伤和修复。骨关节炎是影响美国超过2000万人的主要健康问题，主要是特征是关节关节软骨中承重组织的逐渐变性。该项目旨在使用一组多学科微观成像技术来检测患病软骨的原位分子结构的早期变化。