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

骨关节炎（OA）是老年人的常见病，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改变的原因，但最近的研究表明，炎症介质在关节退化中起重要作用。我们在前期研究（项目编号11671461）中发现OA患者滑膜组织中存在T细胞浸润，患者血清中存在抗骨桥蛋白、YKL-39和中间层蛋白（CILP）的自身抗体。本学期，我们对骨关节炎（OA）的免疫机制进行了进一步的研究，得到了以下结果：炎症反应的存在：补体受体之一C5aR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，它们的受体（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，促进MMP的产生，抑制软骨细胞的蛋白多糖合成1。YKL-39和CILP的致关节炎性：免疫YKL-39和CILP可诱导一些小鼠品系的慢性和轻度关节炎。此外，还研究了责任表位。免疫后组织学表现为滑膜炎、关节受累及异位骨化。pannus样组织的存在：OA软骨表面多见pannus样软组织，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，导致关节进一步降解。未来计划：目前正在研究OA模型动物免疫细胞向正常受试者的转移。

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.