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Novel OA-markers by integrating basic biology and clinic

结合基础生物学和临床的新型 OA 标记物

基本信息

批准号：
7283091
负责人：
Dick K HEINEGARD
金额：
$ 31.27万
依托单位：
LUND UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2003
资助国家：
美国
起止时间：
2003-09-30 至 2010-08-31
项目状态：
已结题

项目摘要

DESCRIPTION(Provided by Applicant): Joint disease like osteoarthritis affects a very large proportion of the population, in the order of 10%, with loss of motion, pain and dysfunction and impaired quality of daily activities. The cost to society rank among the highest for any disease group. Therapy existing today is very limited and largely rely on joint replacement. A prerequisite for development of novel therapy is to delineate mechanisms in the progressive joint destruction as well as novel diagnostic procedures that can identify patients with active disease and evaluate therapy that modifies disease progression. This study is to develop new diagnostic procedures that provide insights in mechanisms in osteoarthritis development and thereby facilitate new advances in therapy as well as provide means for identifying patients at risk and for monitoring therapeutic effects. The specific aims are: 1 ) To define processes in the articular cartilage and bone during development of osteoarthritis by monitoring for release of cartilage and bone constituents; 2) To identify new molecules that show a unique distribution to articular cartilage, meniscus and bone in the joint and have potential as molecular markers of processes affecting these structures; 3) To define specific proteolytic cleavage by the identification of neoepitopes formed by specific proteinases active in cartilage destruction. Specific antibodies developed will be used for assays of processes in the tissue leading to proteolytic release of specific fragments; 4) To search for the identity of enzymes accomplishing specific proteolysis of target molecules; 5) To identify disease mechanisms by focusing on bioactive markers that contain active domains that recognize specific ligands on cells of bone, cartilage and synovium and/or can bind to other factors present in the synovial fluid. Assays will be developed for active fragments and their role in the process in the joint will be investigated; 6) To develop quantitative immunoassays for identified proteins that are altered in articular cartilage of degenerative joint disease; 7) To evaluate newly developed assays by analyses of well defined human patient cohorts as well as animal models with or without specific intervention.

描述（由申请人提供）：骨关节炎等关节疾病影响着很大一部分人口（约 10%），伴有运动丧失、疼痛和功能障碍以及日常活动质量受损。在所有疾病组中，社会成本是最高的。目前现有的治疗方法非常有限，并且很大程度上依赖于关节置换。开发新疗法的先决条件是描述进行性关节破坏的机制以及可以识别患有活动性疾病的患者并评估改变疾病进展的疗法的新诊断程序。这项研究旨在开发新的诊断程序，为骨关节炎发展机制提供见解，从而促进治疗的新进展，并提供识别高危患者和监测治疗效果的方法。具体目标是： 1)通过监测软骨和骨成分的释放来定义骨关节炎发展过程中关节软骨和骨的过程； 2) 识别在关节中的关节软骨、半月板和骨中表现出独特分布的新分子，并有潜力作为影响这些结构的过程的分子标记； 3) 通过鉴定在软骨破坏中具有活性的特定蛋白酶形成的新表位来定义特定的蛋白水解切割。开发的特异性抗体将用于分析组织中导致特定片段蛋白水解释放的过程； 4) 寻找实现目标分子特异性蛋白水解的酶的身份； 5) 通过关注生物活性标记物来确定疾病机制，这些生物活性标记物含有识别骨、软骨和滑膜细胞上的特定配体和/或可以与滑液中存在的其他因子结合的活性结构域。将开发活性片段的测定方法，并研究它们在联合过程中的作用； 6) 开发定量免疫测定法来检测退行性关节病的关节软骨中发生改变的蛋白质； 7) 通过分析明确的人类患者群体以及有或没有特定干预的动物模型来评估新开发的测定方法。

项目成果

期刊论文数量（8）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Short leucine-rich glycoproteins of the extracellular matrix display diverse patterns of complement interaction and activation.

DOI：
10.1016/j.molimm.2008.09.018
发表时间：
2009-02
期刊：
MOLECULAR IMMUNOLOGY
影响因子：
3.6
作者：
Sjoberg, Andreas P.;Manderson, Gavin A.;Morgelin, Matthias;Day, Anthony J.;Heinegard, Dick;Blom, Anna M.
通讯作者：
Blom, Anna M.

Regulation of complement by cartilage oligomeric matrix protein allows for a novel molecular diagnostic principle in rheumatoid arthritis.