Neurophysiological Analysis of Pathogenesis of Synovitis in Osteoarthritic Knees for Development of a New Medical Treatment

探讨神经源性炎症在膝骨关节炎滑膜炎发病中的作用。滑膜组织样本从内侧，外侧滑膜和髌上囊内侧间室骨关节炎膝关节和定位的神经元素在滑膜的免疫化学研究使用的抗体的P物质，降钙素基因相关肽，神经肽Y和血管活性肠肽。P物质阳性的游离神经末梢在内侧区更常见，表现出比外侧区和髌上区更多的树突状形态特征。免疫组化染色结果显示，滑膜内层细胞层中CD 68阳性细胞较多，内侧滑膜下层组织中CD 4和HLA-DR阳性细胞较多，内侧滑膜内层细胞中软骨碎片较多。在体外实验中，P物质刺激T细胞数量增加，其增殖是通过产生IL-2而实现的。在前交叉韧带撕裂和内侧半月板部分切除诱导的骨关节炎动物模型中，切断股神经可使软骨退变更快地进行。提示神经源性炎症反应和T细胞-巨噬细胞相互作用的免疫应答可能是骨关节炎滑膜炎的主要原因。因此，在膝关节骨关节炎的医学治疗中，必须开发与P物质的作用竞争并在神经上保持膝关节内稳态的药物。

The role of neurogenic inflammation in pathogenesis of synovitis in osteoarthritic knees was investigated. Synovial tissue samples were obtained from the medial, lateral synovium and suprapatellar pouch in medial compartmental osteoarthritic knees and localization of neural elements in synovium was immunohistochemically studies using antibodies of substance P, calcitonine gene-related peptide, neuropeptide Y and vasoactive intestinal peptide. Substance P positive free nerve endings were more frequently found in the medial region, which showed more dendritic morphologic features than did those in the lateral and suprapatellar region. Immunohistochemical study of characterization of infiltrated cells in the synovium showed that CD68 positive cells were more abundant in the lining cell laver, and CD4 and HLA-DR positive cells were more often found in the sublsynovial tissue in the medial synovium than those in the lateral, and degenerative cartilage fragments were more entrapped in the medial lining cells. In vitro experiment, T cells exposed to substance P increased in number, whose proliferation was caused by production of IL-2. In animal model of ostoarthritis induced by ACL laceration and partial medial menicectomy, cutting off the femoral nerve brought about more rapid advancement of cartilage degeneration. Overall results indicated that neurogenic inflammation and immunoresponce of T cell-macrophage interaction may be the main cause of synovitis in osteoarthritic knees. Accordingly, in the medical treatment for osteoarthritis of the knee, development of drugs that compete to action of substance P and neurologically keep a homeostasis of a knee joint should be necessitated.