Induction of COX-2 expression by mechanical tension force in human periodontal ligament cells.
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.
Shimizu
N
N
Department of Orthodontics, Nihon University School of Dentistry at Matsudo, Chiba, Japan.
Ozawa
Y
Y
Yamaguchi
M
M
Goseki
T
T
Ohzeki
K
K
Abiko
Y
Y
D016301:Alveolar Bone Loss / Q000209:etiology; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D001732:Bite Force; D002467:Cell Nucleus / Q000201:enzymology; D002478:Cells, Cultured; D002648:Child; D003470:Culture Media; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D003769:Dental Occlusion, Traumatic / Q000209:etiology; D015232:Dinoprostone / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000502:physiology; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D007150:Immunohistochemistry; D018836:Inflammation Mediators / Q000494:pharmacology; D007527:Isoenzymes / Q000235:genetics*; D008297:Male; D008565:Membrane Proteins; D009578:Nitrobenzenes / Q000494:pharmacology; D010510:Periodontal Diseases / Q000209:etiology; D010513:Periodontal Ligament / Q000166:cytology / Q000201:enzymology*; D010544:Peroxidases / Q000037:antagonists & inhibitors / Q000235:genetics*; D011451:Prostaglandin-Endoperoxide Synthases / Q000235:genetics*; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D013314:Stress, Mechanical; D013449:Sulfonamides / Q000494:pharmacology; D013499:Surface Properties; D013997:Time Factors
D000894:Anti-Inflammatory Agents, Non-Steroidal; D003470:Culture Media; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D018836:Inflammation Mediators; D007527:Isoenzymes; D008565:Membrane Proteins; D009578:Nitrobenzenes; D012333:RNA, Messenger; D013449:Sulfonamides; C080955:N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide; D010544:Peroxidases; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; C496511:PTGS1 protein, human; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; D015232:Dinoprostone