title: Cyclic tensile force up-regulates BMP-2 expression through MAP kinase and COX-2/PGE2 signaling pathways in human periodontal ligament cells.
abstract: Periodontal ligament cells play important roles in the homeostasis of periodontal tissue by mechanical stress derived from mastication, such as tension, compression, fluid shear, and hydrostatic force. In the present study, we showed that cyclic tensile force increased the gene expression level of bone morphogenetic protein (BMP)-2, a crucial regulator of mineralization, in human periodontal ligament cells using real-time PCR. Signaling inhibitors, PD98059/U0126 (extracellular signal-regulated kinase (ERK) inhibitors) and SB203580/SB202190 (p38 inhibitors), revealed that tensile force-mediated BMP-2 expression was dependent on activation of the ERK1/2 and p38 mitogen-activated protein (MAP) kinase pathways. Cyclic tensile force also induced cyclooxygenase-2 (COX-2) gene expression in a manner dependent on ERK1/2 and p38 MAP kinase pathways, and induced prostaglandin E2 (PGE2) biosynthesis. NS-398, a COX-2 inhibitor, significantly reduced tensile force-mediated BMP-2 expression, indicating that PGE2 synthesized by COX-2 may be involved in the BMP-2 induction. The inhibitory effect of NS-398 was completely restored by the addition of exogenous PGE2. However, stimulation with PGE2 alone in the absence of tensile force had no effect on the BMP-2 induction, indicating that some critical molecule(s) other than COX-2/PGE2 may be required for cyclic tensile force-mediated BMP-2 induction. Collectively, the results indicate that cyclic tensile force activates ERK1/2 and p38 MAP kinase signaling pathways, and induces COX-2 expression, which is responsible for the sequential PGE2 biosynthesis and release, and furthermore, mediates the increase in BMP-2 expression at the transcriptional level.
authors.affiliation: Department of Periodontology and Endodontology, Tohoku University Graduate School of Dentistry, Sendai 980-8575, Japan.
authors.forename: Risako
authors.initials: R
authors.lastname: Suzuki
authors.affiliation: Department of Periodontology and Endodontology, Tohoku University Graduate School of Dentistry, Sendai 980-8575, Japan. Electronic address: e-nemoto@dent.tohoku.ac.jp.
authors.forename: Eiji
authors.initials: E
authors.lastname: Nemoto
authors.affiliation: Department of Periodontology and Endodontology, Tohoku University Graduate School of Dentistry, Sendai 980-8575, Japan.
authors.forename: Hidetoshi
authors.initials: H
authors.lastname: Shimauchi
mesh_terms: D000328:Adult; D001732:Bite Force; D055396:Bone Morphogenetic Protein 2 / Q000096:biosynthesis / Q000378:metabolism*; D002070:Butadienes / Q000494:pharmacology; D002113:Calcification, Physiologic / Q000502:physiology; D002478:Cells, Cultured; D051546:Cyclooxygenase 2 / Q000096:biosynthesis / Q000378:metabolism*; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D015232:Dinoprostone / Q000096:biosynthesis / Q000378:metabolism*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D005260:Female; D005419:Flavonoids / Q000494:pharmacology; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D008297:Male; D008409:Mastication; D008964:Molar, Third / Q000166:cytology; D009570:Nitriles / Q000494:pharmacology; D009578:Nitrobenzenes / Q000494:pharmacology; D010513:Periodontal Ligament / Q000378:metabolism*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D015398:Signal Transduction; D013312:Stress, Physiological / Q000502:physiology*; D013449:Sulfonamides / Q000494:pharmacology; D015854:Up-Regulation; D055815:Young Adult; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: C525718:BMP2 protein, human; D055396:Bone Morphogenetic Protein 2; D002070:Butadienes; D016861:Cyclooxygenase Inhibitors; D005419:Flavonoids; D007093:Imidazoles; D009570:Nitriles; D009578:Nitrobenzenes; D047428:Protein Kinase Inhibitors; D011725:Pyridines; D013449:Sulfonamides; C113580:U 0126; C080955:N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D048049:Extracellular Signal-Regulated MAP Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D015232:Dinoprostone; C093642:SB 203580; C090942:4-(4-fluorophenyl)-2-(4-hydroxyphenyl)-5-(4-pyridyl)imidazole; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one
keywords: Bone morphogenetic protein 2; Cyclic tensile force; Cyclooxygenase 2; Human periodontal ligament cells; Mitogen-activated protein kinase; Prostaglandin E