title: The effect of BisGMA on cyclooxygenase-2 expression, PGE2 production and cytotoxicity via reactive oxygen species- and MEK/ERK-dependent and -independent pathways.
abstract: After operative restoration, some monomers released from dentin bonding agents or composite resin may induce tissue inflammation and affect the vitality of dental pulp. Whether BisGMA, a major monomer of composite resin, may induce prostaglandin release and cytotoxicity to pulp cells and their mechanisms awaits investigation. We found that BisGMA induced cytotoxicity to human dental pulp cells at concentrations higher than 0.075 mm as analyzed by 3-(4,5-dimethyldiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay. BisGMA (0.1 mm) also stimulated ERK phosphorylation, PGE(2) production, COX-2 mRNA and protein expression as well as ROS production (as indicated by an increase in cellular DCF fluorescence) in dental pulp cells. Catalase (500 and 1000 U/ml) and U0126 (10 and 20 microm, a MEK inhibitor) effectively prevented the BisGMA-induced ERK activation, PGE(2) production and COX-2 expression. Moreover, catalase can protect the pulp cells from BisGMA cytotoxicity, whereas aspirin and U0126 lacked of this protective activity. These results suggest that BisGMA released from composite resin may potentially affect the vitality of dental pulp and induce pulpal inflammation via stimulation of ROS production, MEK/ERK1/2 activation and subsequent COX-2 gene expression and PGE(2) production. Cytotoxicity of BisGMA to dental pulp cells is related to ROS production, but not directly mediated by MEK activation and PGE(2) production.
authors.affiliation: Biomedical Science Team, Chang Gung Institute of Technology, Taoyuan, Taiwan.
authors.forename: Mei-Chi
authors.initials: MC
authors.lastname: Chang
authors.forename: Li-Deh
authors.initials: LD
authors.lastname: Lin
authors.forename: Chiu-Po
authors.initials: CP
authors.lastname: Chan
authors.forename: Hsiao-Hua
authors.initials: HH
authors.lastname: Chang
authors.forename: Lin-I
authors.initials: LI
authors.lastname: Chen
authors.forename: Hsueh-Jen
authors.initials: HJ
authors.lastname: Lin
authors.forename: Hung-Wei
authors.initials: HW
authors.lastname: Yeh
authors.forename: Wan-Yu
authors.initials: WY
authors.lastname: Tseng
authors.forename: Po-Shuen
authors.initials: PS
authors.lastname: Lin
authors.forename: Chiu-Chun
authors.initials: CC
authors.lastname: Lin
authors.forename: Jiiang-Huei
authors.initials: JH
authors.lastname: Jeng
mesh_terms: D000818:Animals; D001241:Aspirin / Q000494:pharmacology; D001672:Biocompatible Materials / Q000737:chemistry / Q000378:metabolism / Q000633:toxicity; D002070:Butadienes / Q000378:metabolism; D002374:Catalase / Q000378:metabolism; D002478:Cells, Cultured; D003188:Composite Resins / Q000737:chemistry / Q000378:metabolism / Q000633:toxicity; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism*; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D003782:Dental Pulp / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D015232:Dinoprostone / Q000096:biosynthesis*; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000378:metabolism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D006146:Guanidines / Q000737:chemistry / Q000378:metabolism / Q000633:toxicity; D006801:Humans; D020935:MAP Kinase Signaling System / Q000502:physiology*; D008422:Materials Testing; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism*; D009570:Nitriles / Q000378:metabolism; D010710:Phosphates / Q000737:chemistry / Q000378:metabolism / Q000633:toxicity; D017382:Reactive Oxygen Species / Q000378:metabolism*
chemical_list: D001672:Biocompatible Materials; D002070:Butadienes; D003188:Composite Resins; D016861:Cyclooxygenase Inhibitors; D004791:Enzyme Inhibitors; D006146:Guanidines; D009570:Nitriles; D010710:Phosphates; D017382:Reactive Oxygen Species; C113580:U 0126; C512060:bisguanidinium hydrogenphosphate monohydrate; D002374:Catalase; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D048049:Extracellular Signal-Regulated MAP Kinases; D020929:Mitogen-Activated Protein Kinase Kinases; D015232:Dinoprostone; D001241:Aspirin