title: Alternation of extracellular matrix remodeling and apoptosis by activation of the aryl hydrocarbon receptor pathway in human periodontal ligament cells.
abstract: It is well known that the aryl hydrocarbon receptor (AhR) is involved in the toxicity of halogenated aromatic hydrocarbons (HAH) and polycyclic aromatic hydrocarbons (PAH). Recent experiments have shown the induction of impaired tooth and hard-tissue formation by AhR pathway activation, however, the effect on periodontal ligament (PDL) tissue remains unclear. Here, we investigated the effects of benzo(a)pyrene (BaP), a member of PAH, on the extracellular matrix (ECM) remodeling-related molecules, collagen type I (COL-I), matrix metalloproteinase-1 (MMP-1), alpha-smooth muscle actin (α-SMA) expression, and apoptosis in two different human periodontal ligament cells (HPDLCs). The transduction of AhR from the cytoplasm to the nucleus and the increase of AhR-responsive genes; that is, cytochrome P450 1A1 (CYP1A1), cytochrome P450 1B1 (CYP1B1), and aryl-hydrocarbon receptor repressor (AhRR), expression was induced by BaP exposure in both HPDLCs. BaP treatment significantly enhanced MMP-1 mRNA expression and MMP-1 protein production, while markedly suppressing COL-I and a-SMA mRNA expression in both HPDLCs. Furthermore, these BaP-treated HPDLCs fell into apoptotic cell death as evidenced by induction in annexin V and caspase-3/7 staining and reduction of total cell number and Bcl-2 mRNA expression. Thus, BaP exposure altered the expression of ECM-related molecules and induced apoptosis in HPDLCs through activation of the AhR pathway. Overactivity of the AhR pathway may induce an inappropriate turnover of PDL tissue via disordered ECM remodeling and apoptosis in PDL cells.
authors.affiliation: Faculty of Dental Science, Division of Oral Rehabilitation, Department of Endodontology and Operative Dentistry, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Tomokiyo
authors.forename: Hidefumi
authors.initials: H
authors.lastname: Maeda
authors.forename: Shinsuke
authors.initials: S
authors.lastname: Fujii
authors.forename: Satoshi
authors.initials: S
authors.lastname: Monnouchi
authors.forename: Naohisa
authors.initials: N
authors.lastname: Wada
authors.forename: Kiyomi
authors.initials: K
authors.lastname: Hori
authors.forename: Katsuaki
authors.initials: K
authors.lastname: Koori
authors.forename: Naohide
authors.initials: N
authors.lastname: Yamamoto
authors.forename: Yoko
authors.initials: Y
authors.lastname: Teramatsu
authors.forename: Akifumi
authors.initials: A
authors.lastname: Akamine
mesh_terms: D000199:Actins / Q000235:genetics / Q000378:metabolism; D000293:Adolescent; D000328:Adult; D017304:Annexin A5 / Q000378:metabolism; D017209:Apoptosis; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics / Q000378:metabolism; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism; D001564:Benzo(a)pyrene / Q000633:toxicity; D053148:Caspase 3 / Q000378:metabolism; D002452:Cell Count; D002460:Cell Line; D002467:Cell Nucleus / Q000235:genetics / Q000378:metabolism; D002470:Cell Survival; D024042:Collagen Type I / Q000235:genetics / Q000378:metabolism; D065633:Cytochrome P-450 CYP1B1; D003593:Cytoplasm / Q000235:genetics / Q000378:metabolism; D004790:Enzyme Induction; D005109:Extracellular Matrix / Q000187:drug effects* / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D020781:Matrix Metalloproteinase 1 / Q000235:genetics / Q000378:metabolism; D010513:Periodontal Ligament / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D018336:Receptors, Aryl Hydrocarbon / Q000378:metabolism*; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D055815:Young Adult
chemical_list: D000199:Actins; D017304:Annexin A5; D001189:Aryl Hydrocarbon Hydroxylases; D051792:Basic Helix-Loop-Helix Proteins; D001564:Benzo(a)pyrene; D053148:Caspase 3; D024042:Collagen Type I; D065633:Cytochrome P-450 CYP1B1; D020781:Matrix Metalloproteinase 1; D012333:RNA, Messenger; D018336:Receptors, Aryl Hydrocarbon; D012097:Repressor Proteins; C541116:ACTA2 protein, human; C492162:AHRR protein, human; C585496:CYP1B1 protein, human; C505407:CASP3 protein, human; C522360:MMP1 protein, human