CARTILAGE AUTOCATABOLISM IN INFECTIOUS ARTHRITIS

感染性关节炎中的软骨自动代谢

基本信息

批准号：
3152132
负责人：
DAVID J SCHURMAN
金额：
$ 8.91万
依托单位：
STANFORD UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
1984
资助国家：
美国
起止时间：
1984-06-01 至 1987-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/3152132
关键词：
O glycosidase Staphylococcus aureus Staphylococcus infection alkaline phosphatase arthritis articular cartilage beta N acetylhexosaminidase beta glucuronidase gel filtration chromatography hyaluronidase organ culture peptidases proteoglycan

项目摘要

The purpose of this grant is to characterize the biochemical basis for articular cartilage autocatabolism. Specifically, we intend to determine what enzymatic activities are responsible for the onset of cartilage destruction. We have shown that bacteria stimulate proteoglycan loss from cartilage if living cartilage cells are present. The initiation of proteoglycan loss is clearly the first step in cartilage destruction. We have established this in animal models of infectious and inflammatory arthritis. Other laboratories have shown that cartilage proteoglycan loss can be triggered by the presence of a low molecular weight protein, catabolin, and that living cartilage is required. The question which remains is what biochemical mechanism supports the proteoglycan degradation. Is it proteolytic? Is it extremely labile or is it present only after some inductive signal for protein synthesis? Are a number of enzymatic activities involved? To answer these questions we are proposing to trigger cartilage degradation by bacteria, Staphylococcus aureus, and after specific times, 12, 24 and 48 hours, to homogenize the cartilage and assay for enzymatic activities. The enzymes to be studied are glucuronidase, hexosaminidase, alkaline phosphatase, cathespin D, neutral proteinases and hyaluronidase. Metabolic inhibitors will be used to study turnover rates and synthesis patterns of enzymatic cartilage degrading enzymes. The significance of this investigation will be to characterize the extent to which cartilage cells alone contribute to arthritis in response to extracellular signals. A cartilage specific response to any foreign stimulus, in conjunction with immune system reactions, may then be additive in cartilage destruction in all forms of arthritis. To effectively control the arthritic reaction, the biochemical characteristics of chondrocyte behavior must first be determined.

这笔赠款的目的是描述生物化学基础关节软骨的自动分解代谢。具体来说，我们打算确定哪些酶活性导致软骨的发生破坏。我们已经证明，如果以下情况，细菌会刺激软骨中的蛋白多糖损失：存在活的软骨细胞。蛋白多糖损失的起始点是显然这是破坏软骨的第一步。我们已经建立了这个在感染性和炎症性关节炎的动物模型中。其他实验室表明，可以引发软骨蛋白多糖损失由于存在低分子量蛋白质，分解代谢蛋白，并且需要活软骨。剩下的问题是什么生化机制支持蛋白多糖降解。是吗蛋白水解？它是否极其不稳定，或者仅在经过一段时间后才出现？蛋白质合成的诱导信号？有多种酶涉及的活动？为了回答这些问题，我们建议触发软骨退化细菌、金黄色葡萄球菌，在特定时间后，12、24 和 48 小时，使软骨均质并测定酶活性。这要研究的酶是葡萄糖醛酸酶、氨基己糖苷酶、碱性酶磷酸酶、组织蛋白酶 D、中性蛋白酶和透明质酸酶。代谢抑制剂将用于研究周转率和合成模式软骨降解酶。这项调查的意义在于表征单独的软骨细胞会导致关节炎细胞外信号。对任何异物的软骨特异性反应刺激与免疫系统反应相结合，可能会起到累加作用各种形式的关节炎中的软骨破坏。为有效控制关节炎反应、软骨细胞生化特性首先必须确定行为。