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性关节炎滑膜炎发病机制中的作用。取内侧间隔性骨性关节炎膝关节内侧滑膜、外侧滑膜和冈上滑膜组织标本，用P物质、降钙素基因相关肽、神经肽Y和血管活性肠肽抗体进行免疫组织化学染色，研究滑膜中神经细胞的定位。P物质阳性神经末梢多见于内侧区，其树突形态特征多于外侧区和冈上区。滑膜浸润细胞的免疫组织化学研究表明，CD68阳性细胞在滑膜衬里细胞层中含量较高，其中内侧滑膜滑膜下组织中CD68阳性细胞多于外侧滑膜组织，退变软骨碎片更多地包裹在内侧滑膜衬里细胞中。在体外实验中，暴露于P物质的T细胞数量增加，其增殖是由IL-2的产生引起的。在前交叉韧带撕裂和内侧半月板部分切除所致的骨性关节炎动物模型中，切断股神经可导致更快的软骨退变。提示神经源性炎症和T细胞-巨噬细胞相互作用的免疫应答可能是膝骨性关节炎滑膜炎症的主要原因。因此，在膝骨性关节炎的医学治疗中，应开发与P物质的作用相竞争的药物，并在神经学上保持膝关节的动态平衡。

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.