Shimizu N, Ozawa Y, Yamaguchi M, Goseki T, Ohzeki K, Abiko Y
Department of Orthodontics, Nihon University School of Dentistry at Matsudo, Chiba, Japan.
J Periodontol. 1998 Jun;69(6):670-7. doi: 10.1902/jop.1998.69.6.670.
Occlusal trauma is caused by excessive occlusal forces and is associated with alveolar bone loss. In the periodontal ligament (PDL), which primarily receives the occlusal force, there is increased prostaglandin E (PGE2) synthesis in response to mechanical stress, and many studies have shown that PGE2 is involved in the pathogenesis of periodontal diseases. Recently, two isozymes of cyclooxygenase, COX-1 and COX-2, which are key enzymes in prostaglandin (PG) biosynthesis, were identified and COX-2 was induced following the activation of cells by a variety of proinflammatory agents. However, the biosynthetic pathway of mechanical stress-dependent PGE2 from PDL cells has not been well understood. When cyclic tension force was applied to human PDL cells (18% increase in surface area), PGE2 release to the culture medium increased in a time-dependent manner. As analyzed by semi-quantitative PCR, COX-2 mRNAs, while hardly detectable in controls, increased dramatically on day 3 and 5 in response to tension force. In contrast, COX-1 mRNAs detected in controls were not affected by tension force. By immunocytochemical staining, COX-2 protein was significantly increased by tension force around the unstained cell nucleus in a time-dependent manner. When NS-398, a selective COX-2 inhibitor, was added to the medium, PGE2 synthesis increased by tension force was completely inhibited. These results indicate that tension force induces COX-2 in human PDL cells and that this induction is responsible for the augmentation of PGE2 production stimulated by tension force. Since selective COX-2 inhibitors have less adverse effects compared with those of non-steroidal anti-inflammatory drugs, they may be of therapeutic benefit for treatment of periodontal disease accompanying traumatic occlusion.
咬合创伤由过大的咬合力引起，并与牙槽骨吸收有关。在主要承受咬合力的牙周膜（PDL）中，机械应力会导致前列腺素E（PGE2）合成增加，许多研究表明PGE2参与牙周疾病的发病机制。最近，鉴定出了环氧化酶的两种同工酶COX-1和COX-2，它们是前列腺素（PG）生物合成中的关键酶，并且在多种促炎剂激活细胞后COX-2会被诱导。然而，牙周膜细胞中机械应力依赖性PGE2的生物合成途径尚未完全清楚。当对人牙周膜细胞施加周期性张力（表面积增加18%）时，PGE2向培养基中的释放呈时间依赖性增加。通过半定量PCR分析，COX-2 mRNA在对照组中几乎检测不到，但在第3天和第5天因张力而显著增加。相比之下，对照组中检测到的COX-1 mRNA不受张力影响。通过免疫细胞化学染色，COX-2蛋白在未染色的细胞核周围因张力而呈时间依赖性显著增加。当向培养基中添加选择性COX-2抑制剂NS-398时，张力引起的PGE2合成增加被完全抑制。这些结果表明，张力可诱导人牙周膜细胞中的COX-2，并且这种诱导作用导致了张力刺激下PGE2产生的增加。由于选择性COX-2抑制剂与非甾体抗炎药相比副作用较小，它们可能对治疗伴有创伤性咬合的牙周疾病具有治疗益处。
