JOINT AGING AND OSTEOARTHRITIS

尽管它是人类残疾的主要原因，但 骨关节炎的发病机制仍有待于 足够的细节以允许理性的方法来逮捕其 无论是进步还是预防。因为它主要是一种疾病 在以后的生活中会影响到大部分人，一些 老龄化进程的各个方面必须为其发展奠定基础。 这项建议汇集了来自世界各地的个人的专业知识。 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、年龄相关变化方面的技能 成分、代谢活性、体液反应和遗传 兔和人关节结构的表达及其影响 在这些测量中得出不同阶段的骨关节炎。 还将与通过以下方法获得的信号进行关联 成像和光谱模式下的核磁共振 目的是提高我们使用这一非 早期诊断的侵入性程序。美国政府各部门 代表的大学包括：化学、外科、放射学、 医学与儿科学及斯克里普斯临床与研究 基金会，临床免疫学分部。 软骨钙质沉着症与骨性关节炎的频繁关联 随着年龄的增长而逐渐增加，因此有理由 进一步勾勒出高血糖的潜在代谢基础 软骨细胞、成纤维细胞和软骨细胞的焦磷酸含量 从受感染患者培养的淋巴母细胞 这是加州大学圣迭戈分校首次观察到的一种软骨钙质沉着症。关于的报道 2种嘌呤核苷酸降解酶的活性增强 在其中一些患者中，嘌呤合成参与了 一种含嘌呤类药物的细胞复制和疗效 最近报告的代理，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。至 区分中介的内在因素和外在因素 骨性关节炎的发展，他们将调查 不同类型软骨细胞的反应性差异 在培养中以激素、神经肽、细胞因子、生长因子为主。 抗氧化剂和各种化学试剂以及诱导剂 蛋白水解酶胶原酶及其功能的调控 抑制剂。所产生的基本信息有希望 提供合理的方法来开发和监控 新的治疗药物，其临床目标是改善 骨性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.