Treponema denticola increases MMP-2 expression and activation in the periodontium via reversible DNA and histone modifications.
Treponema denticola increases MMP-2 expression and activation in the periodontium via reversible DNA and histone modifications.
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DOI：
10.1111/cmi.12815
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发表时间：
2018-04
影响因子：
3.4
通讯作者：
Fenno JC
中科院分区：
文献类型：
--
作者：
Ateia IM;Sutthiboonyapan P;Kamarajan P;Jin T;Godovikova V;Kapila YL;Fenno JC
宿主衍生的基质金属蛋白酶（MMP）和细菌蛋白酶介导牙周炎中细胞外基质和支撑牙槽骨的破坏。密螺旋体牙菌素蛋白酶诱导牙周膜 (PDL) 细胞中 MMP-2 的表达和激活，而牙菌素介导的 pro-MMP-2 激活是细胞纤连蛋白降解所必需的。在这里，我们报道 T. denticola 通过牙周组织的表观遗传修饰来调节 MMP-2 的表达。在 T. denticola 攻击之前或之后用表观遗传酶抑制剂处理 PDL 细胞。分别通过免疫印迹、酶谱分析和 qRT-PCR 评估纤连蛋白片段化、MMP-2 表达和激活。使用基因阵列评估 T. denticola 攻击的 PDL 细胞和牙周组织中的染色质修饰酶表达。几类表观遗传酶在患病组织和 T. denticola 攻击的 PDL 细胞中显示出显着的转录变化。在用极光激酶和组蛋白脱乙酰酶抑制剂处理的 PDL 细胞中，T. denticola 介导的 MMP-2 表达和激活显着降低。相比之下，DNA甲基转移酶抑制剂几乎没有作用，而组蛋白乙酰转移酶、甲基转移酶和去甲基酶的抑制剂则加剧了T. denticola介导的MMP-2表达和激活。由牙周菌或其他口腔微生物介导的牙周组织的慢性表观遗传变化可能导致慢性牙周炎常规治疗的成功有限，并且可能导致治疗逆转。
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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DOI：
10.1016/j.bbrc.2012.11.087
发表时间：
2013-01-04
影响因子：
3.1
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DOI：
10.3390/molecules19033149
发表时间：
2014-03-13
期刊：
Molecules (Basel, Switzerland)
影响因子：
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