PROTEOGLYCAN MEASUREMENT IN OSTEOARTHRITIS IN VIVO

体内骨关节炎的蛋白聚糖测量

• 批准号: 6171133
• 负责人: Ravinder Reddy
• 金额: $ 30.07万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-09-01 至 2002-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6171133
• 关键词: animal tissue; articular cartilage; bioimaging /biomedical imaging; biomarker; cytokine; diagnosis design /evaluation; diagnostic tests; disease /disorder model; dogs; histology; immunocytochemistry; magnetic resonance imaging; musculoskeletal disorder diagnosis; noninvasive diagnosis; osteoarthritis; proteoglycan; sodium ion; spectrometry

DESCRIPTION (Adapted from Applicant's Abstract): Osteoarthritis is a major cause of morbidity in the population over 50, affecting more than 40 million Americans. It also imposes considerable expense on the health care system. There is currently no cure for this debilitating disease and the effective treatment is, at best, focused on symptomatic relief. Cartilage degeneration is thought to be the primary pathology associated with the disease. Recent developments in chondro-protective drugs and gene therapy have generated substantial demand for noninvasive techniques for detecting changes in cartilage. These developments and any other potential therapies can effectively work only if the disease is detected early. Among the most significant early changes in articular cartilage in osteoarthritis is the loss of proteoglycans (PG). However, currently there is no reliable quantitative noninvasive method available for detecting and evaluating these early changes. The applicants proposed to quantitatively evaluate the potential of sodium magnetic resonance imaging (MRI) for detecting and quantifying proteoglycan (PG) changes in an in vivo model of early osteoarthritis. To accomplish this task, the applicants proposed to first characterize the technique in bovine cartilage specimens treated with a known mediator of extracellular matrix degradation. Secondly, they would inject to cytokine injection based model of PG degradation in the dog knee to create artificial osteoarthritic condition and measure dose dependent changes in cartilage degeneration. Specifically, they proposed to inject the cytokine into the intra-articular space of the hind limb knee, using the contralateral knee as control. After the appropriate time interval, the applicants proposed to perform sodium MR on both the treated and control knee to measure changes in sodium content. After the MRI experiments, harvested cartilage tissue would be subjected to spectrophotometric, histologic, and immunohistochemistry determination of PG content and its spatial distribution. The changes in sodium content as measured from MRI and the changes in PG content (measured by spectrophotometry, histology and immunohistochemistry) would be correlated. These measurements would establish the capability of sodium MR in determining the changes that occur during early degeneration of cartilage in vivo. Since it is possible to perform sodium MR in a noninvasive clinical setting, this method can be immediately exploited in human studies for detecting early changes due to QA. Once developed, this method would have a major impact on the ability to make an early and appropriate therapeutic intervention, monitor the clinical outcome, and aid in evaluating new treatment modalities.

描述（改编自申请人的摘要）：骨关节炎是一种主要的 50 岁以上人口发病的原因，影响超过 4000 万人 美国人。它还给医疗保健系统带来了相当大的开支。 目前尚无治愈这种使人衰弱的疾病的有效方法 治疗充其量只是缓解症状。软骨退变是 被认为是与该疾病相关的主要病理学。最近的 软骨保护药物和基因治疗的发展已产生 对用于检测变化的非侵入性技术的巨大需求 软骨。这些发展和任何其他潜在的疗法可以有效地 只有及早发现疾病才有效。其中最重要的早期 骨关节炎中关节软骨的变化是蛋白多糖的损失 （PG）。但目前尚无可靠的定量无创方法 可用于检测和评估这些早期变化。申请人 提议定量评估钠磁共振的潜力 用于检测和量化体内蛋白多糖 (PG) 变化的成像 (MRI) 早期骨关节炎的体内模型。为了完成这项任务，申请人 提议首先在牛软骨标本中表征该技术 用已知的细胞外基质降解介质处理。第二， 他们将注射到基于细胞因子注射的 PG 降解模型中 狗膝盖创造人工骨关节炎状况并测量剂量 软骨退化的依赖性变化。具体来说，他们建议 将细胞因子注射到后肢膝盖的关节内空间，使用 以对侧膝关节作为对照。经过适当的时间间隔后， 申请人建议对治疗膝关节和对照膝关节进行钠 MR 测量钠含量的变化。经过 MRI 实验后，收获 软骨组织将进行分光光度、组织学和 免疫组化测定PG含量及其空间分布。 MRI 测量的钠含量变化和 PG 变化 含量（通过分光光度法、组织学和免疫组织化学测定） 将是相关的。这些测量将建立以下能力： 钠 MR 确定早期退化过程中发生的变化 体内的软骨。由于可以在无创的情况下进行钠 MR 临床环境中，该方法可以立即用于人体研究 检测由于 QA 引起的早期变化。一旦开发出来，该方法将具有 对早期和适当治疗的能力产生重大影响 干预、监测临床结果并帮助评估新治疗 方式。