JOINT AGING AND OSTEOARTHRITIS

尽管它是人类残疾的主要原因， 骨关节炎的发病机制仍有待确定， 足够的细节，以允许合理的方法来逮捕其 或者是预防。 因为它主要是一种疾病 影响了大部分人口的晚年生活， 老龄化过程的一个方面必须为其发展奠定基础。 这项建议汇集了来自广泛的个人的专业知识， 一系列学科，从磁共振成像和 分子遗传学，以临床医学和骨科为重点 他们在结构生物学、化学和生物学领域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 兔和人关节结构的表达及其作用 骨关节炎的不同阶段。 相关性也将与获得的信号， 成像和光谱模式的核磁共振 目的是提高我们利用这种非- 早期诊断侵入性手术。各部门 大学代表包括：化学，外科，放射学， 医学和儿科，来自斯克里普斯诊所和研究 基金会，临床免疫学分部。 软骨钙质沉着症与骨关节炎的频繁联系 随着年龄的增长而逐渐增加，因此， 进一步阐明高血压的潜在代谢基础 软骨细胞、成纤维细胞和 淋巴母细胞培养的患者受影响， 软骨钙质沉着症，这是在加州大学圣地亚哥分校首次发现的。 报告 嘌呤核苷酸降解的2种酶的活性增加 在这些患者中，嘌呤合成的参与， 细胞复制和含嘌呤治疗剂的功效 代理商最近报告说，提供了详细测试的充分理由 这些细胞类型中嘌呤代谢的改变。 到 区分内在和外在因素介导 骨关节炎的发展，他们将研究 不同类型软骨细胞的反应性差异 激素、神经肽、细胞因子、生长因子。 抗氧化剂和各种化学试剂以及诱导 和调节蛋白水解酶胶原酶及其 抑制剂的 生成的基本信息保证 提供合理的方法来发展和监测 新的治疗药物的临床目的是改善 骨关节炎的早期诊断和治疗。

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.