Treponema denticola increases MMP-2 expression and activation in the periodontium via reversible DNA and histone modifications

被引:24
作者
Ateia, Islam M. [1 ,5 ]
Sutthiboonyapan, Pimchanok [1 ,6 ]
Kamarajan, Pachiyappan [1 ,4 ]
Jin, Taocong [2 ]
Godovikova, Valentina [3 ]
Kapila, Yvonne L. [1 ,4 ]
Fenno, J. Christopher [3 ]
机构
[1] Univ Michigan, Sch Dent, Dept Periodont & Oral Med, Ann Arbor, MI 48109 USA
[2] Univ Michigan, Sch Dent, Res Off, Ann Arbor, MI 48109 USA
[3] Univ Michigan, Sch Dent, Dept Biol & Mat Sci, Ann Arbor, MI 48109 USA
[4] Univ Calif San Francisco, Sch Dent, Dept Orofacial Sci, San Francisco, CA 94143 USA
[5] Univ Mansoura, Dept Periodont & Oral Med, Fac Dent, Mansoura, Egypt
[6] Chulalongkorn Univ, Dept Periodontol, Fac Dent, Bangkok, Thailand
关键词
AURORA KINASE INHIBITOR; FIBRONECTIN FRAGMENTS MODULATE; CHYMOTRYPSIN-LIKE PROTEASE; HEPARIN-BINDING DOMAIN; MAJOR SURFACE PROTEIN; MATRIX METALLOPROTEINASES; LIGAMENT CELLS; PORPHYROMONAS-GINGIVALIS; EPIGENETIC MECHANISMS; GENE-EXPRESSION;
D O I
10.1111/cmi.12815
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Host-derived matrix metalloproteinases (MMPs) and bacterial proteases mediate destruction of extracellular matrices and supporting alveolar bone in periodontitis. The Treponema denticola dentilisin protease induces MMP-2 expression and activation in periodontal ligament (PDL) cells, and dentilisin-mediated activation of pro-MMP-2 is required for cellular fibronectin degradation. Here, we report that T. denticola regulates MMP-2 expression through epigenetic modifications in the periodontium. PDL cells were treated with epigenetic enzyme inhibitors before or after T. denticola challenge. Fibronectin fragmentation, MMP-2 expression, and activation were assessed by immunoblot, zymography, and qRT-PCR, respectively. Chromatin modification enzyme expression in T. denticola-challenged PDL cells and periodontal tissues were evaluated using gene arrays. Several classes of epigenetic enzymes showed significant alterations in transcription in diseased tissue and T. denticola-challenged PDL cells. T. denticola-mediated MMP-2 expression and activation were significantly reduced in PDL cells treated with inhibitors of aurora kinases and histone deacetylases. In contrast, DNA methyltransferase inhibitors had little effect, and inhibitors of histone acetyltransferases, methyltransferases, and demethylases exacerbated T. denticola-mediated MMP-2 expression and activation. Chronic epigenetic changes in periodontal tissues mediated by T. denticola or other oral microbes may contribute to the limited success of conventional treatment of chronic periodontitis and may be amenable to therapeutic reversal.
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页数:17
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