title: Effect of the Acidic Dental Resin Monomer 10-methacryloyloxydecyl Dihydrogen Phosphate on Odontoblastic Differentiation of Human Dental Pulp Cells.
abstract: Although 10-methacryloyloxydecyl dihydrogen phosphate (10-MDP) is frequently used as an acidic resin monomer in dental adhesives, its effect on dental pulp cells (DPCs) has been rarely reported. The purpose of this study was to examine the effects of 10-MDP on the inflammatory response and odontoblastic differentiation of DPCs at minimally toxic concentrations. We found that 10-MDP caused the release of inflammatory cytokines including NO, PGE2, iNOS, COX-2, TNF-α, IL-1β, IL-6 and IL-8 in a concentration-dependent manner. In addition, 10-MDP reduced alkaline phosphatase activity, mineralization nodule formation and mRNA expression of odontoblastic differentiation markers such as dentin sialophosphoprotein, dentin matrix protein-1, osterix and Runx2 in a concentration-dependent manner with low toxicity. In addition, 10-MDP induced activation of nuclear factor-E2-related factor 2 (Nrf2) and its target gene, haeme oxygenase-1 (HO-1). We evaluated whether the effect of 10-MDP was related to the induction of HO-1 and found that treatment with a selective inhibitor of HO-1 reversed the production of 10-MDP-mediated pro-inflammatory cytokines and the inhibition of differentiation markers. Pre-treatment with either a GSH synthesis inhibitor or antioxidants blocked 10-MDP-induced mitogen-activated protein kinases (MAPKs), Nrf2 and NF-κB pathways. Taken together, the results of this study showed that minimally toxic concentrations of 10-MDP promoted an inflammatory response and suppressed odontoblastic differentiation of DPCs by activating Nrf2-mediated HO-1 induction through MAPK and NF-κB signalling.
authors.affiliation: Department of Oral and Maxillofacial Pathology & Research Center for Tooth and Periodontal Tissue Regeneration (MRC), School of Dentistry, Kyung Hee University, Seoul, Korea.
authors.forename: Eun-Cheol
authors.initials: EC
authors.lastname: Kim
authors.affiliation: Department of Conservative Dentistry, School of Dentistry, Kyung Hee University, Seoul, Republic of Korea.
authors.forename: Haejin
authors.initials: H
authors.lastname: Park
authors.affiliation: Department of Dental Hygiene, School of Health Sciences, Dankook University, Cheonan, Republic of Korea.
authors.forename: Sang-Im
authors.initials: SI
authors.lastname: Lee
authors.affiliation: Department of Conservative Dentistry, School of Dentistry, Kyung Hee University, Seoul, Republic of Korea.
authors.forename: Sun-Young
authors.initials: SY
authors.lastname: Kim
mesh_terms: D000975:Antioxidants / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects*; D002460:Cell Line; D016207:Cytokines / Q000276:immunology / Q000378:metabolism; D003782:Dental Pulp / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004790:Enzyme Induction; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005786:Gene Expression Regulation; D051547:Heme Oxygenase-1 / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics; D006801:Humans; D018836:Inflammation Mediators / Q000276:immunology / Q000378:metabolism; D008689:Methacrylates / Q000633:toxicity*; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D051267:NF-E2-Related Factor 2 / Q000235:genetics / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D009804:Odontoblasts / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D011671:Pulpitis / Q000139:chemically induced* / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D019279:Resin Cements / Q000633:toxicity*; D015398:Signal Transduction / Q000187:drug effects; D013997:Time Factors
chemical_list: D000975:Antioxidants; D016207:Cytokines; D004791:Enzyme Inhibitors; D018836:Inflammation Mediators; D008689:Methacrylates; D051267:NF-E2-Related Factor 2; D016328:NF-kappa B; C495635:NFE2L2 protein, human; D012333:RNA, Messenger; D019279:Resin Cements; C069749:methacryloyloxydecyl dihydrogen phosphate; C496541:HMOX1 protein, human; D051547:Heme Oxygenase-1; D020928:Mitogen-Activated Protein Kinases