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Aggregatibacter actinomycetemcomitans lipopolysaccharide regulates bone sialoprotein gene transcription
Author(s) -
Li Xinyue,
Zhou Liming,
Takai Hideki,
Sasaki Yoko,
Mezawa Masaru,
Li Zhengyang,
Wang Zhitao,
Yang Li,
Wang Shuang,
Matsumura Hiroyoshi,
Kaneko Takashi,
Yoshimura Atsutoshi,
Ogata Yorimasa
Publication year - 2012
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.24157
Subject(s) - bone sialoprotein , aggregatibacter actinomycetemcomitans , runx2 , chemistry , osteoblast , microbiology and biotechnology , creb , osteocalcin , lipopolysaccharide , porphyromonas gingivalis , transcription factor , periodontitis , biology , immunology , medicine , gene , alkaline phosphatase , biochemistry , in vitro , enzyme
Aggregatibacter actinomycetemcomitans ( A. actinomycetemcomitans ) is believed to be associated with aggressive periodontitis characterized by a rapid bone loss. A. actinomycetemcomitans lipopolysaccharide (LPS) has a similar structure to Escherichia coli LPS, and they are Toll‐like receptor 4 agonists. Bone sialoprotein (BSP) is an early marker of osteoblast differentiation. To investigate the effects of A. actinomycetemcomitans LPS on bone formation, we targeted BSP as a marker for osteogenic differentiation and bone formation. BSP mRNA levels were decreased by 0.1 µg/ml and increased by 0.01 µg/ml A. actinomycetemcomitans LPS at 6 h in osteoblast‐like ROS17/2.8 cells. In transient transfection analyses, 0.1 µg/ml decreased and 0.01 µg/ml A. actinomycetemcomitans LPS increased luciferase activities of the construct (−116 to +60). Introduction of 2 bp mutations to the constructs showed that the effects of A. actinomycetemcomitans LPS were mediated by a cAMP response element (CRE), a FGF2 response element (FRE), and a homeodomain protein‐binding site (HOX). Tyrosine kinase, ERK1/2, and PI3‐kinase/Akt participated in the effects of both 0.1 and 0.01 µg/ml A. actinomycetemcomitans LPS. The results of gel shift showed that 0.1 µg/ml decreased while 0.01 µg/ml A. actinomycetemcomitans LPS increased CRE‐, FRE‐, and HOX‐binding protein complexes formation at 6 h, and revealed that 0.01 µg/ml A. actinomycetemcomitans LPS induced BSP transcription through CREB1, JunD, Fra2, c‐Fos, Runx2, Dlx5, and Smad1 targeting those response elements. These studies therefore indicated that 0.1 µg/ml suppressed and 0.01 µg/ml A. actinomycetemcomitans LPS increased BSP gene transcription mediated through CRE, FRE, and HOX elements in the rat BSP gene promoter. J. Cell. Biochem. 113: 2822–2834, 2012. © 2012 Wiley Periodicals, Inc.