NMR Spectral Markers of Cartilage Degeneration in Osteoarthritis

骨关节炎软骨退变的核磁共振谱标记

• 批准号: 7738537
• 负责人: Xiaojuan Li
• 金额: $ 20.86万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-08-01 至 2011-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7738537
• 关键词: Affect; Age; American; Biochemical; Biochemical Markers; Biochemistry; Biological Assay; Biomechanics; Cadaver; Cartilage; Cartilage Matrix; Clinical; Clinical Management; Collagen; Data; Degenerative Disorder; Degenerative polyarthritis; Development; Diagnostic; Diffusion; Disease; Early Diagnosis; Functional disorder; Future; Gills; Goals; Harvest; Health; Histology; Human; Hydroxyproline; Image; Imaging Techniques; In Situ; Knee; Lead; Magic; Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; Measurement; Measures; Metabolic; Methods; Molecular; NMR Spectroscopy; Obesity; Ontario; Osteoarthrosis Deformans; Outcome; Pain; Patient Care; Patients; Pharmaceutical Preparations; Physiologic pulse; Prevalence; Proteoglycan; Protocols documentation; Protons; Recovery; Relaxation; Reproducibility; Research; Resolution; Sampling; Societies; Specimen; Spectrum Analysis; Techniques; Time; Tissues; Treatment Efficacy; Water; aggrecan; articular cartilage; base; clinical care; clinically significant; disability; genetic profiling; improved; in vivo; knee replacement arthroplasty; new therapeutic target; novel; novel therapeutics; prevent; public health relevance; quantum; research study; tool; two-dimensional

DESCRIPTION (provided by applicant): Osteoarthritis (OA) is a major health concern with very limited treatment options. Understanding biochemical and molecular changes in OA cartilage can provide clues for new therapeutic targets. Furthermore, there is clearly a need for in vivo imaging techniques that can non-invasively and critically evaluate the therapeutic efficacy of new treatment methods. Magnetic resonance imaging (MRI) has been used to study cartilage degeneration by observing the changes in water content, relaxation and diffusion. However, these changes are indirect by-products of alterations in proteoglycan (PG)/collagen matrix in degenerative cartilage, and do not provide direct measures of biochemical changes. This is the gap our research is intended to fill. High Resolution - Magic Angle Spinning (HRMAS) spectroscopy is a unique non-destructive ex vivo technique that can provide direct measurement of biochemical changes in tissues. However, studies using HRMAS in human cartilage are very limited and no relationship between biochemical changes measured by HRMAS and cartilage degeneration has been established. Our long-term goal is to develop non-invasive imaging markers for early degeneration of cartilage. The goal of this proposal is to develop and validate ex vivo HRMAS techniques for evaluating biochemical changes in cartilage matrix associated with OA. The central hypothesis is that the non-destructive imaging capability of HRMAS will lead to identification of spectroscopic markers of early cartilage degeneration that can be related to the molecular changes in osteoarthritic cartilage matrix such as PG/collagen degradation. This research is an essential first step in the development of a novel, in vivo, non-invasive diagnostic tool that provides direct measurement of cartilage biochemistry for early OA. Specifically, we will 1) establish and optimize HRMAS acquisition protocols in human cartilage; 2) identify biochemical changes associated with cartilage degeneration using HRMAS. Cartilage samples will be harvested from OA patients who undergo total knee replacement and cadaver knees (controls). Cartilage degeneration will be evaluated using histology. HRMAS measurement between control and OA samples will be compared and HRMAS spectral markers for cartilage degeneration will be identified. HRMAS measurement will be correlated with PG and collagen assay quantitation as well as with immnohistochemical analysis on aggrecan and collagen cleavage neoepitopes. This project is novel in developing and applying ex vivo HRMAS techniques to characterize biochemical changes in human OA cartilage. The future extension of this to in vivo MR spectroscopy is what makes this study clinically significant and exciting. PUBLIC HEALTH RELEVANCE: Osteoarthritis (OA) affects more than 25 million Americans and is one of the leading causes of disability. Current treatment to OA is very limited and diagnosis of early cartilage degeneration remains a challenge. This proposal aims at developing a novel ex vivo NMR method to explore spectral markers for cartilage degeneration in OA. This research is an essential first step in the development of a novel, non-invasive, diagnostic tool that provides direct measurement of cartilage biochemistry for early OA, which will significantly improve patient management and clinical care of OA.

描述（由申请人提供）：骨关节炎（OA）是一个主要的健康问题，治疗选择非常有限。了解OA软骨中的生化和分子变化可以为新的治疗靶点提供线索。此外，显然需要能够非侵入性地和批判性地评估新治疗方法的治疗功效的体内成像技术。磁共振成像（MRI）已被用于研究软骨退变，通过观察水含量，松弛和扩散的变化。然而，这些变化是退行性软骨中蛋白聚糖（PG）/胶原基质改变的间接副产物，不能直接测量生化变化。这正是我们的研究所要填补的差距。高分辨率魔角旋转（HRMAS）光谱是一种独特的非破坏性离体技术，可以直接测量组织中的生化变化。然而，在人类软骨中使用HRMAS的研究非常有限，并且尚未建立HRMAS测量的生化变化与软骨退化之间的关系。我们的长期目标是开发软骨早期退变的非侵入性成像标记物。本提案的目的是开发和验证用于评估OA相关软骨基质生化变化的离体HRMAS技术。中心假设是HRMAS的非破坏性成像能力将导致早期软骨退化的光谱标记物的鉴定，其可以与骨关节炎软骨基质中的分子变化（例如PG/胶原降解）相关。这项研究是开发一种新的体内非侵入性诊断工具的重要第一步，该工具可直接测量早期OA的软骨生物化学。具体来说，我们将1）建立和优化人类软骨的HRMAS采集方案; 2）使用HRMAS识别与软骨退行性变相关的生化变化。将从接受全膝关节置换术的OA患者和尸体膝关节（对照）中采集腕关节样本。将使用组织学评价软骨变性。将比较对照和OA样本之间的HRMAS测量值，并识别软骨退化的HRMAS光谱标记物。HRMAS测量将与PG和胶原测定定量以及与聚集蛋白聚糖和胶原裂解新表位的免疫组织化学分析相关。该项目是新颖的，在开发和应用离体HRMAS技术来表征人类OA软骨的生化变化。未来将其扩展到体内MR波谱是使这项研究具有临床意义和令人兴奋的原因。公共卫生相关性：骨关节炎（OA）影响超过2500万美国人，是残疾的主要原因之一。目前对OA的治疗非常有限，早期软骨退变的诊断仍然是一个挑战。该提案旨在开发一种新的离体NMR方法，以探索OA中软骨退变的光谱标记物。这项研究是开发一种新型、非侵入性诊断工具的重要第一步，该工具可直接测量早期OA的软骨生物化学，这将显著改善OA的患者管理和临床护理。