title: Camphorquinone inhibits odontogenic differentiation of dental pulp cells and triggers release of inflammatory cytokines.
abstract: BACKGROUND
  Camphorquinone (CQ) is a photoinitiator that triggers polymerization of light-curing materials such as dental adhesives and composites. CQ does not become a part of the polymer network, suggesting that CQ can be leached out into surrounding environment including dental pulp and exert adversary effects on tissues. In order to understand the mechanisms of CQ-induced side effects, we investigated the effect of CQ on cell viability, cytokine secretion, and odontogenic differentiation of dental pulp stem cells in vitro.
  
  
  METHODS
  Cell viability was assessed using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay after CQ exposure. Western blotting was performed for p16(INK4A), p21(WAF1), and p53. Secretory cytokines were evaluated using the membrane-enzyme-linked immunosorbent assay as well as conventional and quantitative reverse-transcription polymerase chain reaction. The effects of CQ on odontogenic differentiation were evaluated using alkaline phosphatase and alizarin red S staining methods.
  
  
  RESULTS
  CQ treatment suppressed the proliferation of DPSCs and induced the expression of p16(INK4A), p21(WAF1), and p53. Levels of proinflammatory cytokines (eg, interleukin 6, interleukin 8, and matrix metalloproteinase-3 [MMP3]) were increased by CQ treatment. CQ also inhibited odontogenic differentiation and mineralization capacities of DPSC and MC3T3-E1 cells.
  
  
  CONCLUSIONS
  Our study showed that CQ may trigger pulpal inflammation by inducing proinflammatory cytokine production from the pulpal cells and may impair odontogenic differentiation of dental pulp cells, resulting in pulpal irritation and inflammation.
authors.affiliation: UCLA School of Dentistry, Los Angeles, California, USA. rkim@dentistry.ucla.edu
authors.forename: Reuben H
authors.initials: RH
authors.lastname: Kim
authors.forename: Drake W
authors.initials: DW
authors.lastname: Williams
authors.forename: Susan
authors.initials: S
authors.lastname: Bae
authors.forename: Rachel S
authors.initials: RS
authors.lastname: Lee
authors.forename: Ju-Eun
authors.initials: JE
authors.lastname: Oh
authors.forename: Shebli
authors.initials: S
authors.lastname: Mehrazarin
authors.forename: Tony
authors.initials: T
authors.lastname: Kim
authors.forename: Ki-Hyuk
authors.initials: KH
authors.lastname: Shin
authors.forename: No-Hee
authors.initials: NH
authors.lastname: Park
authors.forename: Mo K
authors.initials: MK
authors.lastname: Kang
mesh_terms: D016475:3T3 Cells; D000469:Alkaline Phosphatase / Q000032:analysis; D000818:Animals; D000880:Anthraquinones; D015153:Blotting, Western; D002164:Camphor / Q000031:analogs & derivatives* / Q000633:toxicity; D002454:Cell Differentiation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004396:Coloring Agents; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000032:analysis; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000032:analysis; D016207:Cytokines / Q000187:drug effects* / Q000378:metabolism; D003764:Dental Materials / Q000633:toxicity; D003782:Dental Pulp / Q000166:cytology / Q000187:drug effects*; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism*; D015850:Interleukin-6 / Q000032:analysis; D016209:Interleukin-8 / Q000032:analysis; D008422:Materials Testing; D019278:Matrix Metalloproteinase 3 / Q000032:analysis; D008689:Methacrylates / Q000633:toxicity; D051379:Mice; D009805:Odontogenesis / Q000187:drug effects*; D058567:Photoinitiators, Dental / Q000633:toxicity*; D013778:Tetrazolium Salts; D013844:Thiazoles; D014074:Tooth Calcification / Q000187:drug effects; D016159:Tumor Suppressor Protein p53 / Q000032:analysis
chemical_list: D000880:Anthraquinones; C493956:CDKN1A protein, human; D004396:Coloring Agents; D019941:Cyclin-Dependent Kinase Inhibitor p16; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016207:Cytokines; D003764:Dental Materials; D018836:Inflammation Mediators; D015850:Interleukin-6; D016209:Interleukin-8; D008689:Methacrylates; D058567:Photoinitiators, Dental; C495901:TP53 protein, human; D013778:Tetrazolium Salts; D013844:Thiazoles; D016159:Tumor Suppressor Protein p53; C004468:Alizarin Red S; C005044:hydroxyethyl methacrylate; D002164:Camphor; D000469:Alkaline Phosphatase; C511768:MMP3 protein, human; D019278:Matrix Metalloproteinase 3; C022616:thiazolyl blue; C553149:camphorquinone