ヒト軟骨細胞における2-カルバ環状ホスファチジン酸の抗炎症作用について

抄録

Osteoarthritis (OA) is a common joint disease characterized by the breakdown of subchondral bone and cartilage damage, most often affecting middle-aged and elderly people. Although the etiology of OA is still unknown, some reports suggest that inflammatory factors such as interleukin (IL)-1β mediate the progression of OA. In order to investigate the effect of IL-1β and the possibility of treatment for OA, we used 2-carba-cyclic phosphatidic acid (2ccPA) and its derivatives on human chondrocytes. 2ccPA is a synthesized phospholipid based from a bioactive phospholipid mediator: cyclic phosphatidic acid (cPA). It is previously reported that 2ccPA exhibits anti-inflammatory and chondroprotective effects on an OA animal model. 2ccPA and its ring-opened body (ROB) derivative significantly suppressed IL-1β-induced upregulation of IL-6, matrix metalloproteinase-13, and cyclooxygenase-2, as well as the degradation of type II collagen and aggrecan. However, the other two derivatives, the deacylated body and the ring-opened deacylated body showed little effect on IL-1β-exposed human chondrosarcoma cell-line. These data suggest that acyl chain of 2ccPA and ROB is essential for anti-inflammatory effect on OA. Taken together, this study provides evidence that 2ccPA and ROB would be a novel therapeutic agent for OA.