Treponema denticola upregulates MMP-2 activation in periodontal ligament cells: interplay between epigenetics and periodontal infection.
Treponema denticola upregulates MMP-2 activation in periodontal ligament cells: interplay between epigenetics and periodontal infection.
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Treponema Denticola上调牙周韧带细胞中的MMP-2激活：表观遗传学和牙周感染之间的相互作用。
DOI：
10.1016/j.archoralbio.2014.06.003
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发表时间：
2014-10
影响因子：
3
通讯作者：
Fenno, J. Christopher
中科院分区：
文献类型：
--
作者：
Miao, Di;Godavikava, Valentina;Qian, Xu;Seshadrinathan, Suchithra;Kapila, Yvonne L.;Fenno, J. Christopher
牙周病原体引发慢性炎症和组织稳态失调，这是牙周病的特征。为了更好地了解口腔微生物与宿主组织的相互作用，我们研究了龋密螺旋体攻击后牙周韧带细胞中MMP-2的表达和激活。培养后的PDL细胞用齿状分枝杆菌攻毒，分别用免疫荧光显微镜观察细菌的粘附、内化和存活情况，用抗生素保护实验观察细菌的存活情况。酶谱法检测MMP-2活化。采用qRT-PCR方法检测齿状赤霉素攻毒后MMP-2、MT1/MMP和TIMP-2的表达。通过甲基化敏感限制性内切分析和亚硫酸盐DNA测序筛选MMP-2和MT1/MMP启动子甲基化。齿状木耳粘附于PDL细胞并被其内化，但在细胞内存活时间不超过24小时。重要的是，尽管牙齿菌攻击后PDL培养上清液中的牙本质素活性逐渐下降，但MMP-2的激活持续了5天，这表明参与了其他调节机制。MT1/MMP和TIMP-2的转录和表达均随赤霉素的侵袭而增加。然而，与先前报道的PDL细胞中组成性MMP-2前表达一致，MMP-2启动子被低甲基化，独立于齿状霉的攻击。在PDL细胞中，MMP-2启动子低甲基化与组成性MMP-2前表达一致。这与牙牙菌介导的mmp -2相关基因上调和mmp -2前基因的慢性激活相结合，模拟了牙周病慢性的关键体内机制，特别是mmp -2依赖的基质降解和骨吸收。粘着性和/或内化可能通过一种或多种调节机制参与这些过程，包括接触依赖性信号转导或其他表观遗传机制。
Periodontal pathogens initiate chronic dysregulation of inflammation and tissue homeostasis that characterize periodontal disease. To better understand oral microbe - host tissue interactions, we investigated expression and activation of MMP-2 in periodontal ligament cells following Treponema denticola challenge. Cultured PDL cells were challenged with T. denticola, and bacterial adherence, internalization and survival were assayed by immunofluorescence microscopy and antibiotic protection assays, respectively. MMP-2 activation was detected by zymography. MMP-2, MT1/MMP and TIMP-2 expression following T. denticola challenge was determined by qRT-PCR. Promoter methylation of MMP-2 and MT1/MMP was screened by methylation-sensitive restriction analysis and by bisulfite DNA sequencing. T. denticola adhered to and was internalized by PDL cells but did not survive intracellularly beyond 24 hours. Importantly, while dentilisin activity in PDL culture supernatants gradually decreased following T. denticola challenge, MMP-2 activation persisted for up to 5 days, suggesting involvement of other regulatory mechanisms. Transcription and expression of MT1/MMP and TIMP-2 increased in response to T. denticola challenge. However, consistent with previously reported constitutive pro-MMP-2 expression in PDL cells, the MMP-2 promoter was hypomethylated, independent of T. denticola challenge. MMP-2 promoter hypomethylation is consistent with constitutive pro-MMP-2 expression in PDL cells. This, coupled with T. denticola-mediated upregulation of MMP-2-related genes and chronic activation of pro-MMP-2, mimics key in vivo mechanisms of periodontal disease chronicity, in particular MMP-2-dependent matrix degradation and bone resorption. Adherence and/or internalization of T. denticola may contribute to these processes by one or more regulatory mechanisms, including contact-dependent signal transduction or other epigenetic mechanisms.
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影响因子：
4.2
作者：
Joseph, Jeena;Kapila, Yvonne L.;Kapila, Sunil
通讯作者：
Kapila, Sunil
影响因子：
3.1
作者：
HAAPASALO, M;SINGH, U;UITTO, VJ
通讯作者：
UITTO, VJ
影响因子：
4.8
作者：
Chernov, Andrei V.;Sounni, Nor Eddine;Strongin, Alex Y.
通讯作者：
Strongin, Alex Y.
影响因子：
3.1
作者：
Godovikova, Valentina;Goetting-Minesky, M. Paula;Fenno, J. Christopher
通讯作者：
Fenno, J. Christopher
影响因子：
3.1
作者：
Euzebio Alves, Vanessa Tubero;Bueno da Silva, Henrique Aparecido;Holzhausen, Marinella
通讯作者：
Holzhausen, Marinella