Functional effects of antibodies to collagen on cartilage synthesis and degradation

胶原蛋白抗体对软骨合成和降解的功能影响

• 批准号: nhmrc : 143549
• 负责人: A/Pr Merrill Rowley
• 金额: $ 15.14万
• 依托单位: Monash University
• 依托单位国家: 澳大利亚
• 项目类别: NHMRC Project Grants
• 财政年份: 2001
• 资助国家: 澳大利亚
• 起止时间: 2001-01-01 至 2003-12-31
• 项目状态: 已结题
• 来源: https://researchdata.edu.au/functional-effects-antibodies-synthesis-degradation/77666
• 关键词: Functional; effects; antibodies; collagen; cartilage

It has been shown that antibodies to collagen type II in cartilage occur in ~70% of patients with early rheumatoid arthritis, suggesting that autoimmunity to cartilage collagen may play a part in the devleopment of this destructive arthritis. An animal model widely used as a model of human RA is the disease collagen induced arthritis (CIA). It is induced by immunisation of mice with collagen II; antibodies to collagen II are critical for the development of CIA. However not all such antibodies are disease-associated. There may be particular regions on the collagen molecule where antibody-binding causes damage. This project is based on the hypothesis that antibodies to collagen type II, which transfer arthritis in mice, are those that react specifically with regions of the collagen fibrils that are crucial for cartilage stability and function. We plan to test this hypothesis in an in vitro system using cultured cartilage. We predict, based on our preliminary data, that antibodies to collagen II from mice with CIA will interfere with the normal assembly and structure of cartilage. We will test this by adding antibodies under precisely defined conditions to cultured cartilage, and analysing the matrix that is synthesised. The study would then be extended to RA with a comparison of the regions of collagen II that react with antibodies of mouse and human origin. Showing that antibodies to collagen II are directly destructive, allowing for an understanding of their site and mode of action, would greatly advance our understanding of the cause of RA and would lead to more effective forms of treatment.

已经表明，软骨中II型胶原蛋白的抗体出现在约70%的早期类风湿性关节炎患者中，这表明对软骨胶原蛋白的自身免疫可能在这种破坏性关节炎的发展中起作用。广泛用作人RA模型的动物模型是疾病胶原诱导的关节炎（CIA）。它是通过用胶原蛋白II免疫小鼠诱导的;胶原蛋白II的抗体对CIA的发展至关重要。然而，并非所有这些抗体都与疾病相关。胶原蛋白分子上可能存在抗体结合导致损伤的特定区域。该项目是基于这样的假设，即转移小鼠关节炎的II型胶原蛋白抗体是那些与对软骨稳定性和功能至关重要的胶原纤维区域特异性反应的抗体。我们计划在体外系统中使用培养的软骨来测试这一假设。根据我们的初步数据，我们预测，CIA小鼠的II型胶原抗体会干扰软骨的正常组装和结构。我们将通过在精确定义的条件下向培养的软骨中添加抗体并分析合成的基质来测试这一点。然后，该研究将扩展到RA，比较与小鼠和人类来源的抗体反应的胶原蛋白II区域。显示胶原蛋白II的抗体是直接破坏性的，允许了解它们的作用部位和模式，将大大推进我们对RA病因的理解，并将导致更有效的治疗形式。