title: Benzo[a]pyrene/aryl hydrocarbon receptor signaling inhibits osteoblastic differentiation and collagen synthesis of human periodontal ligament cells.
abstract: OBJECTIVE
  Cigarette smoking has detrimental effects on periodontal tissue, and is known to be a risk factor for periodontal disease, including the loss of alveolar bone and ligament tissue. However, the direct effects of cigarette smoking on periodontal tissue remain unclear. Recently, we demonstrated that benzo[a]pyrene (BaP), which is a prototypic member of polycyclic aryl hydrocarbons and forms part of the content of cigarettes, attenuated the expression of extracellular matrix remodeling-related genes in human periodontal ligament (PDL) cells (HPDLCs). Thus, we aimed to examine the effects of BaP on the osteoblastic differentiation and collagen synthesis of HPDLCs.
  
  
  METHODS
  HPDLCs were obtained from healthy molars of three patients, and quantitative reverse transcription-polymerase chain reaction were performed for gene expression analyses of cytochrome P450 1A1 and 1B1, alkaline phosphatase, bone sialoprotein and aryl hydrocarbon receptor (AhR), a receptor for polycyclic aryl hydrocarbons. We have also analyzed the role of the AhR, using 2-methyl-2H-pyrazole-3-carboxylic acid (2-methyl-4-o-tolylazo-phenyl)-amide (CH-223191), which is an AhR antagonist.
  
  
  RESULTS
  The treatment of HPDLCs with BaP reduced mRNA expression of osteogenic genes, alkaline phosphatase activity, mineralization and collagen synthesis. The treatment with CH-223191 subsequently restored the observed suppressive effects of BaP on HPDLCs.
  
  
  CONCLUSIONS
  The present results suggest that BaP exerts inhibitory effects on the maintenance of homeostasis in HPDL tissue, such as osteoblastic differentiation and collagen synthesis of HPDLCs, and that this signaling pathway could be suppressed by preventing the transactivity of AhR. Future studies may unveil a role for the inhibition of AhR as a promising therapeutic agent for periodontal disease caused by cigarette smoking.
authors.affiliation: Division of Oral Rehabilitation, Department of Endodontology and Operative Dentistry, Faculty of Dental Science, Kyushu University, Fukuoka, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Monnouchi
authors.affiliation: Department of Endodontology, Kyushu University Hospital, Fukuoka, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Maeda
authors.affiliation: Division of Oral Rehabilitation, Department of Endodontology and Operative Dentistry, Faculty of Dental Science, Kyushu University, Fukuoka, Japan.
authors.forename: A
authors.initials: A
authors.lastname: Yuda
authors.affiliation: Division of Oral Rehabilitation, Department of Endodontology and Operative Dentistry, Faculty of Dental Science, Kyushu University, Fukuoka, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Serita
authors.affiliation: Department of Endodontology, Kyushu University Hospital, Fukuoka, Japan.
authors.forename: N
authors.initials: N
authors.lastname: Wada
authors.affiliation: Department of Endodontology, Kyushu University Hospital, Fukuoka, Japan.
authors.forename: A
authors.initials: A
authors.lastname: Tomokiyo
authors.affiliation: Division of Oral Rehabilitation, Department of Endodontology and Operative Dentistry, Faculty of Dental Science, Kyushu University, Fukuoka, Japan.|Department of Endodontology, Kyushu University Hospital, Fukuoka, Japan.
authors.forename: A
authors.initials: A
authors.lastname: Akamine
mesh_terms: D001564:Benzo(a)pyrene / Q000494:pharmacology; D002454:Cell Differentiation / Q000502:physiology; D002478:Cells, Cultured; D003094:Collagen / Q000096:biosynthesis*; D006801:Humans; D010006:Osteoblasts / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D010513:Periodontal Ligament / Q000166:cytology / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D018336:Receptors, Aryl Hydrocarbon / Q000378:metabolism* / Q000502:physiology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D059467:Transcriptome
chemical_list: D018336:Receptors, Aryl Hydrocarbon; D001564:Benzo(a)pyrene; D003094:Collagen
keywords: aryl hydrocarbon receptor; benzo[a]pyrene; periodontal ligament