Alternation of extracellular matrix remodeling and apoptosis by activation of the aryl hydrocarbon receptor pathway in human periodontal ligament cells

作者：Tomokiyo Atsushi; Maeda Hidefumi^*; Fujii Shinsuke; Monnouchi Satoshi; Wada Naohisa; Hori Kiyomi; Koori Katsuaki; Yamamoto Naohide; Teramatsu Yoko; Akamine Akifumi

来源：Journal of Cellular Biochemistry, 2012, 113(10): 3093-3103.

DOI：10.1002/jcb.24186

• PERIODONTAL LIGAMENT
• ARYL HYDROCARBON RECEPTOR
• MATRIX METALLOPROTEINASE-1
• COLLAGEN TYPE I
• ALPHA-SMOOTH MUSCLE ACTIN

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 (a-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. J. Cell. Biochem. 113: 30933103, 2012.

• 出版日期2012-10