PROTEOGLYCAN METABOLISM IN OSTEOARTHRITIS

骨关节炎中的蛋白聚糖代谢

• 批准号: 2080003
• 负责人: BRUCE CATERSON
• 金额: $ 16.18万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 1990
• 资助国家: 美国
• 起止时间: 1990-07-06 至 1995-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2080003
• 关键词: biomarker; chondroitin sulfates; cytokine; disease /disorder model; early diagnosis; enzyme linked immunosorbent assay; guinea pigs; human tissue; immunocytochemistry; immunologic techniques; monoclonal antibody; osteoarthritis; pathology; protein metabolism; proteoglycan; radioimmunoassay; remission /regression; western blottings

Osteoarthritis is a slowly progressive destructive disease of the joints which is widespread in man and other animal species. The underlying cause(s) of osteoarthritis have not been identified despite numerous histological, biochemical and biomechanical studies examining the changes that occur as the disease develops. In humans, osteoarthritis takes years to develop and at present the disease cannot be diagnosed until quite late in the degenerative process. Thus current medical treatment consists of mainly trying to reverse the later, inflammatory stage of the disease. At present there is a particular need for methods detecting the early stages of osteoarthritis so that factors lead to the cartilage destruction can be better understood. In this proposal we describe preliminary data identify- ing, in osteoarthritic cartilage proteoglycans, the occurrence of struc- tural "markers" that are indicative of the initial biochemical changes leading to the onset of osteoarthritis. These markers consist of atypical structures in the chondroitin sulfate (CS) glycosaminoglycans of osteoarth- ritic proteoglycans. The objectives of this proposal are to further investigate this novel finding. The specific aims to achieve this objec- tive will be: 1. To determine the relative occurrence of atypical CS structures in proteoglycans from normal and osteoarthritic human cartilage using monoclonal antibodies that specifically recognize these structures. 2. To perform similar studies in two animal models that mimic the onset of osteoarthritis in man, i.e., the development of spontaneous OA. 3. To further characterize the specificity of monoclonal antibodies that recog- nize atypical CS structures and develop immunoassay procedures to measure the expression of these atypical CS structures in cartilage, serum and/or synovial fluid. 4. To perform in vitro cell culture studies to inves- tigate the biosynthesis of proteoglycans containing these atypical struc- tures, and to see cytokines and growth factors modulate the expression of these structures. 5. To perform immunohistochemical studies on normal and osteoarthritic cartilage to establish if focal or general expression of the epitopes occur in OA. Overall, the studies outlined in this proposal should lead to a better understanding of factors involved in the onset of osteoarthritis and may lead to the development of means for halting or reversing the disease process.

骨关节炎是一种缓慢进行的关节破坏性疾病 在人类和其他动物中广泛存在。 底层 骨关节炎的原因尚未确定，尽管有许多 组织学、生物化学和生物力学研究检查变化 随着疾病的发展而发生。 在人类，骨关节炎需要数年时间 目前这种疾病直到很晚才能被诊断出来 在退化的过程中。 因此，目前的医疗包括 主要是试图逆转疾病的晚期炎症阶段。 在 目前特别需要检测早期阶段的方法 骨关节炎，使因素导致软骨破坏可以 更好地理解。 在本提案中，我们描述了初步数据识别- 在骨关节炎软骨蛋白多糖中， 指示初始生化变化的自然“标记” 导致骨关节炎的发作。 这些标志物包括非典型的 骨关节炎的硫酸软骨素（CS）糖胺聚糖中的结构- 关键蛋白聚糖。 这项建议的目的是进一步 调查这一新发现。 实现这一目标的具体目标是： 这将是：1。 确定非典型CS的相对发生率 正常和骨关节炎人软骨蛋白多糖的结构 使用特异性识别这些结构的单克隆抗体。 2. 为了在两种动物模型中进行类似的研究， 人的骨关节炎，即，自发性OA的发展。 3. 到 进一步表征识别的单克隆抗体的特异性， 识别非典型CS结构，并开发免疫测定程序， 这些非典型CS结构在软骨、血清和/或 滑液 4. 进行体外细胞培养研究以研究- 抑制含有这些非典型结构的蛋白聚糖的生物合成， tures，并查看细胞因子和生长因子调节表达的 这些结构。 5. 对正常和 骨关节炎软骨，以确定是否局灶性或普遍表达的 表位存在于OA中。 总的来说，本提案中概述的研究 应该导致更好地了解参与发病的因素， 骨关节炎，并可能导致发展的手段，停止或 逆转疾病进程。

项目成果

Monoclonal antibodies that detect biochemical markers of arthritis in humans.

• DOI: 10.1002/art.1780380513
• 发表时间: 1995-05
• 期刊: Arthritis and rheumatism
• 作者: R. R. Slater-R.;M. Bayliss;P. Lachiewicz;D. Visco;B. Caterson

Expression of proteoglycan epitopes in articular cartilage repair tissue.

关节软骨修复组织中蛋白多糖表位的表达。

• 发表时间: 1998
• 期刊: The Iowa orthopaedic journal
• 作者: Lin,PP;Buckwalter,JA;Olmstead,M;Caterson,B
• 通讯作者: Caterson,B

Osteoarthritis in cynomolgus macaques. II. Detection of modulated proteoglycan epitopes in cartilage and synovial fluid.

食蟹猴的骨关节炎。

• DOI: 10.1002/jor.1100130314
• 发表时间: 1995
• 期刊: Journal of orthopaedic research : official publication of the Orthopaedic Research Society
• 作者: Carlson,CS;Loeser,RF;Johnstone,B;Tulli,HM;Dobson,DB;Caterson,B
• 通讯作者: Caterson,B

Catabolism of aggrecan by explant cultures of human articular cartilage in the presence of retinoic acid.

在视黄酸存在下通过人关节软骨的外植体培养物进行聚集蛋白聚糖的分解代谢。

• DOI: 10.1006/abbi.1995.1431
• 发表时间: 1995
• 期刊: Archives of biochemistry and biophysics.
• 作者: Ilic,MZ;Mok,MT;Williamson,OD;Campbell,MA;Hughes,CE;Handley,CJ
• 通讯作者: Handley,CJ