Epigenetic Modifications of Histones in Periodontal Disease
Epigenetic Modifications of Histones in Periodontal Disease
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DOI：
10.1177/0022034515611876
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发表时间：
2016-02-01
影响因子：
7.6
通讯作者：
Castilho, R. M.
中科院分区：
文献类型：
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作者：
Martins, M. D.;Jiao, Y.;Castilho, R. M.
牙周炎是一种慢性感染性疾病，由微生态失调引起，微生态失调是牙周细菌和宿主生物之间的失衡。牙周炎是成年人牙齿脱落的主要原因，约占美国人口的50%。除了与治疗牙周炎相关的临床挑战之外，这种疾病的进展和慢性性质严重影响人类健康。新出现的证据表明，牙周炎与细菌诱导的蛋白质和组织降解以外的机制有关。在这里，我们假设细菌能够通过组蛋白修饰介导口腔上皮细胞的表观遗传修饰。在这项研究中，我们发现体内生态失调导致表观遗传修饰，包括组蛋白的乙酰化和DNA甲基转移酶1的下调。此外，在体外口腔上皮细胞暴露于脂多糖导致组蛋白修饰，转录辅激活因子，如p300/CBP的激活，和核因子-κ B（NF-κ B）的积累。鉴于口腔上皮细胞是牙周组织抵御细菌的第一道防线，我们还评估了病原体识别受体的激活是否诱导组蛋白修饰。我们发现Toll样受体1、2和4以及核苷酸结合寡聚化结构域蛋白1的激活可诱导口腔上皮细胞中的组蛋白乙酰化。我们的研究结果证实了新兴的概念，表观遗传修饰在牙周炎的发展中发挥作用。
Periodontitis is a chronic infectious disease driven by dysbiosis, an imbalance between commensal bacteria and the host organism. Periodontitis is a leading cause of tooth loss in adults and occurs in about 50% of the US population. In addition to the clinical challenges associated with treating periodontitis, the progression and chronic nature of this disease seriously affect human health. Emerging evidence suggests that periodontitis is associated with mechanisms beyond bacteria-induced protein and tissue degradation. Here, we hypothesize that bacteria are able to induce epigenetic modifications in oral epithelial cells mediated by histone modifications. In this study, we found that dysbiosis in vivo led to epigenetic modifications, including acetylation of histones and downregulation of DNA methyltransferase 1. In addition, in vitro exposure of oral epithelial cells to lipopolysaccharides resulted in histone modifications, activation of transcriptional coactivators, such as p300/CBP, and accumulation of nuclear factor-kappa B (NF-kappa B). Given that oral epithelial cells are the first line of defense for the periodontium against bacteria, we also evaluated whether activation of pathogen recognition receptors induced histone modifications. We found that activation of the Toll-like receptors 1, 2, and 4 and the nucleotide-binding oligomerization domain protein 1 induced histone acetylation in oral epithelial cells. Our findings corroborate the emerging concept that epigenetic modifications play a role in the development of periodontitis.