Influence of immune mechanism on aging in articular cartilage, -Immune response and responsible proteins in osteoarthritis-

免疫机制对关节软骨老化的影响，-骨关节炎中的免疫反应和相关蛋白-

基本信息

批准号：
13671547
负责人：
NAKAMURA Hiroshi
金额：
$ 2.05万
依托单位：
St. Marianna University School of Medicine
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2001
资助国家：
日本
起止时间：
2001 至 2002
项目状态：
已结题

项目摘要

Osteoarthritis (OA) is frequent during aged population and is caused by damage of articular cartilage. As far, :aging or mechanical stress have been considered to be a cause of articular change, however recent studies show that inflammatory mediators have an important role in the articular degradation. As a result of our previous study (project No. 11671461), we showed that T cells infiltrated into synovial tissue from patients with OA and autoantibodies against osteopontin, YKL-39 and intermediate layer protein (CILP) were present in sera of the patients. In this term, the immune mechanism in osteoarthritis (OA) was investigated further and following results were obtained.1. The presence of inflammatory reactions : C5aR, one of compliment receptors was expressed in OA chondrocytes. Chemokines such as MCP-1, MIP-1 and RANTES are secreted from articular chondrocytes and their receptors (CCR2 and CCR5) were expressed in chondrocytes. Among these, RANTES and MCP-1 had catabolic effects on articular cartilage enhancing MMP production and suppressing proteoglycan synthesis from chondrocytes.1. Arthritogenicity of YKL-39 and CILP : Immunization of YKL-39 and CILP induced chronic and oligo-arthritis in some mouse strains. Moreover, responsible epitopes were investigated. Histrologically, synovitis and articular involvement were shown and ectopic ossification was found following CILP immunization.1. The presence of pannus-like tissue : Pannus-like soft tissue was frequently found on the surface of OA cartilage and the tissue had catabolic characteristics expressing IL-1 and MMP-3.1. Interaction of chondrocytes with T cells : Direct contact of chondrocytes with autologous T cells enhanced MMP and RANTES production leading further articular degradation.1. Future plan : Transfer of immune cells from OA model animals to normal subjects are investigated at present.

骨关节炎（OA）在老年人中很常见，是由关节软骨损伤引起的。到目前为止，衰老或机械应力被认为是关节变化的原因，但最近的研究表明炎症介质在关节退化中起着重要作用。我们之前的研究（项目号 11671461）表明，T 细胞浸润到 OA 患者的滑膜组织中，并且患者血清中存在针对骨桥蛋白、YKL-39 和中间层蛋白 (CILP) 的自身抗体。本学期对骨关节炎(OA)的免疫机制进行了进一步的研究，得到以下结果： 1．炎症反应的存在：C5aR，补体受体之一在OA软骨细胞中表达。趋化因子如MCP-1、MIP-1和RANTES由关节软骨细胞分泌，其受体（CCR2和CCR5）在软骨细胞中表达。其中，RANTES和MCP-1对关节软骨具有分解代谢作用，增强MMP的产生并抑制软骨细胞蛋白多糖的合成。1． YKL-39 和 CILP 的致关节炎性：YKL-39 和 CILP 的免疫在一些小鼠品系中诱导慢性关节炎和寡关节炎。此外，还研究了相关表位。 CILP免疫后组织学显示滑膜炎和关节受累，并发现异位骨化。1．血管翳样组织的存在：OA软骨表面经常发现血管翳样软组织，并且该组织具有表达IL-1和MMP-3.1的分解代谢特征。软骨细胞与T细胞的相互作用：软骨细胞与自体T细胞的直接接触增强了MMP和RANTES的产生，导致进一步的关节退化。1．未来计划：目前正在研究将OA模型动物的免疫细胞转移到正常受试者中。