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Transcriptional regulation of bone sialoprotein gene by Porphyromonas gingivalis lipopolysaccharide
Author(s) -
Li Xinyue,
Kato Naoko,
Mezawa Masaru,
Li Zhengyang,
Wang Zhitao,
Yang Li,
Sasaki Yoko,
Kaneko Takashi,
Takai Hideki,
Yoshimura Atsutoshi,
Ogata Yorimasa
Publication year - 2010
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.22594
Subject(s) - porphyromonas gingivalis , bone sialoprotein , microbiology and biotechnology , chemistry , tlr4 , lipopolysaccharide , response element , protein kinase b , creb , receptor , promoter , transcription factor , signal transduction , biology , endocrinology , medicine , osteocalcin , gene expression , periodontitis , biochemistry , gene , alkaline phosphatase , enzyme
Abstract Lipopolysaccharide (LPS) is a major mediator of inflammatory response. Periodontopathic bacterium Porphyromonas gingivalis LPS has quite different character from Escherichia coli LPS. E. coli LPS is agonist for Toll‐like receptor 4 (TLR4), whereas P. gingivalis LPS worked as antagonist for TLR4. Bone sialoprotein (BSP) is an early marker of osteoblast differentiation. To investigate the effects of P. gingivalis LPS on BSP transcription, we used rat osteoblast‐like ROS17/2.8 cells. BSP mRNA levels were decreased by 0.1 µg/ml and increased by 0.01 µg/ml P. gingivalis LPS at 12 h. Results of luciferase assays showed that 0.1 µg/ml decreased and 0.01 µg/ml P. gingivalis LPS increased BSP transcription in −116 to +60 BSP construct. The effects of P. gingivalis LPS were abrogated by double mutations in cAMP response element (CRE) and FGF2 response element (FRE). Tyrosine kinase inhibitor herbimycin A, ERK1/2 inhibitor and antioxidant N ‐acetylcystein inhibited effects of P. gingivalis LPS. Protein kinase A inhibitor and PI3‐kinase/Akt inhibitor only abolished the effect of 0.01 µg/ml P. gingivalis LPS. Furthermore, 0.1 µg/ml LPS decreased the CRE– and FRE–protein complexes formation, whereas 0.01 µg/ml P. gingivalis LPS increased the nuclear protein binding to CRE and FRE. ChIP assays revealed increased binding of CREB1, JunD, Fra2, Runx2, Dlx5, and Smad1 to a chromatin fragment containing the CRE and FRE by 0.01 µg/ml P. gingivalis LPS. These studies therefore indicated that 0.1 µg/ml suppressed, and 0.01 µg/ml P. gingivalis LPS increased BSP gene transcription mediated through CRE and FRE elements in the rat BSP gene promoter. J. Cell. Biochem. 110: 823–833, 2010. © 2010 Wiley‐Liss, Inc.