JOINT AGING AND OSTEOARTHRITIS

关节老化和骨关节炎

• 批准号: 3091197
• 负责人: J E SEEGMILLER
• 金额: $ 68.94万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 1988
• 资助国家: 美国
• 起止时间: 1988-12-01 至 1992-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3091197
• 关键词: aging; cartilage; joint disorder; osteoarthritis

Despite its position as a major cause of human disability, the pathogenesis of osteoarthritis still remains to be defined in sufficient detail to permit a rational approach to arresting its progress or to its prevention. Since it is primarily a disease affecting a major segment of the population in later life, some aspect of the aging process must set the stage for its development. This proposal marshalls the expertise of individuals from a wide range of disciplines, ranging from magnetic resonance imaging and molecular genetics, to clinical medicine and orthopedics to focus their skills on age-related changes in structural biology, chemical composition, metabolic activity, humoral response and genetic expression of both rabbit and human joint structures and the effect of various stages of osteoarthritis on these measurements. Correlations will also be made with the signals obtained with nuclear magnetic resonance in both imaging and spectroscopic modes with the objective of enhancing our ability to use this non- invasive procedure for early diagnosis. The departments of the University represented include: Chemistry, Surgery, Radiology, Medicine and Pediatrics and from Scripps Clinic and Research Foundation, the Division of Clinical Immunology. The frequent association of chondrocalcinosis with osteoarthritis increases progressively with advancing age, thus giving reason for further delineation of the underlying metabolic basis for the high pyrophosphate content of cartilage cells, fibroblasts and lymphoblasts cultured from patients affected with chondrocalcinosis, an observation first made at UCSD. Reports of an increased activity of 2 enzymes of purine nucleotide degradation in some of these patients, the involvement of purine synthesis in cell replication and efficacy of a purine-containing therapeutic agent recently reported, provides good reason for detailed tests for alterations in purine metabolism in these cell types. To distinguish between intrinsic and extrinsic factors mediating development of osteoarthritis, they will investigate the differences in responsiveness of different types of chondrocytes in culture to hormones, neuropeptides, cytokines, growth factors. anti-oxidants and various chemical agents as well as the induction and regulation of the proteolytic enzyme collagenase and its inhibitors. The basic information generated holdS promise of providing rational approaches to the development and monitoring of new therapeutic agents with the clinical objective of improving the early diagnosis and treatment of osteoarthritis.

尽管它是人类残疾的主要原因，但 骨关节炎的发病机理仍然有待定义 足够的细节允许采用合理的方法来逮捕其 进步或预防。 因为它主要是一种疾病 影响后来的主要人口，有些人 衰老过程的各个方面必须为其发展奠定基础。 该提议使个人的专业知识来自 学科范围，从磁共振成像和 分子遗传学，临床医学和骨科的聚焦 他们在结构生物学，化学上与年龄相关的变化方面的技能 组成，代谢活性，体液反应和遗传 兔子和人类关节结构的表达以及效果 这些测量的各个骨关节炎阶段。 相关性也将与获得的信号建立 成像和光谱模式中的核磁共振 目的是增强我们使用这种非 - 早期诊断的侵入性程序。部门 大学代表包括：化学，手术，放射学， 医学和儿科以及来自Scripps诊所和研究 基金会，临床免疫学部。 软骨钙化与骨关节炎的经常关联 随着年龄的增长而逐步增加 进一步描述高的基础代谢基础 软骨细胞，成纤维细胞和 受影响的患者培养的淋巴细胞 软骨钙化，这是UCSD首次进行的观察。 报告 嘌呤核苷酸降解的2种酶的活性增加 在其中一些患者中，嘌呤合成参与 含嘌呤的治疗的细胞复制和功效 代理商最近报告，提供了详细测试的充分理由 用于这些细胞类型中嘌呤代谢的改变。 到 区分介导的内在和外在因素 骨关节炎的发展，他们将调查 不同类型软骨细胞的反应性差异 在激素，神经肽，细胞因子，生长因子中培养。 抗氧化剂和各种化学剂以及诱导 和蛋白水解酶胶原酶及其的调节 抑制剂。 生成的基本信息有望 为开发和监视提供合理的方法 新的治疗剂的临床目的是改善 早期诊断和治疗骨关节炎。