Role of neuropeptide, substance-p, on the mechanisms of joint destruction in rheumatoid arthritis.

临床证据表明，周围神经系统可能参与炎症的病理生理过程。神经肽物质P （SP）存在于周围感觉神经的无髓鞘C纤维中，据报道，它可能是慢性炎症的介质之一，因为它在发炎的关节中被检测到，并对间充质细胞有各种生物学作用。也有报道称SP可诱导类风湿性关节炎患者滑膜细胞的胶原酶释放。然而，SP是否直接诱导关节软骨退化仍是未知的。因此，我们在体外研究了SP对关节软骨细胞基质金属蛋白酶释放和硫酸糖胺聚糖积累的影响。外源性SP处理导致单层培养牛关节软骨细胞金属蛋白酶释放增加。10^<-9> M孵育48h后，细胞凋亡显著增加（p<0.05）。同时，SP对关节软骨细胞的硫酸糖胺聚糖合成无影响。上述结果提示，SP可能通过增加炎性关节炎中金属蛋白酶的释放而加速关节软骨的恶化。

Clinical evidences have suggested that the peripheral nervous system might be involved in the pathophysiology of inflammation. The neuropeptide substance P (SP), which has been found in unmyelinated C fiber of the peripheral sensory nerve, is reported to be one of the possible mediators of chronic inflammation, since it has been detected in inflamed joints and has various biological effects on mesenchymal cells. It is also reported that SP induced collagenase release of synoviocytes obtained from patients with rheumatoid arthritis. However, whether or not SP induces articular cartilage degradation directly, remains unknown. Therefore we have investigated the effect of SP on matrix metalloproteinase release and the accumulation of sulfated glycosaminoglycan of the articular chondrocyte in vitro.Administration of exogenous SP resulted in the increase of metalloproteinase release in the monolayr cultured bovine articular chondrocytes. Significant increase (p<0.05) was observed at the concentration of 10^<-9> M for 48h incubation. Meanwhile SP had no effect on sulfated glycosaminoglycan synthesis of the articular chondrocyte. These results suggest that SP may increase the deterioration of articular cartilage through augmentation of the release of metalloproteinase in inflammatory arthritis.