title: Induction of COX-2 expression by mechanical tension force in human periodontal ligament cells.
abstract: 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.
authors.affiliation: Department of Orthodontics, Nihon University School of Dentistry at Matsudo, Chiba, Japan.
authors.forename: N
authors.initials: N
authors.lastname: Shimizu
authors.forename: Y
authors.initials: Y
authors.lastname: Ozawa
authors.forename: M
authors.initials: M
authors.lastname: Yamaguchi
authors.forename: T
authors.initials: T
authors.lastname: Goseki
authors.forename: K
authors.initials: K
authors.lastname: Ohzeki
authors.forename: Y
authors.initials: Y
authors.lastname: Abiko
mesh_terms: 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
chemical_list: 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