Campos Kelma, Gomes Carolina Cavalieri, Farias Lucyana Conceição, Silva Renato Menezes, Letra Ariadne, Gomez Ricardo Santiago
Department of Oral Surgery and Pathology, School of Dentistry, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.
Department of Pathology, Biological Sciences Institute, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.
J Endod. 2016 Jan;42(1):127-30. doi: 10.1016/j.joen.2015.10.002. Epub 2015 Nov 6.
Matrix metalloproteinases (MMPs) are the major class of enzymes responsible for degradation of extracellular matrix components and participate in the pathogenesis of periapical inflammatory lesions. MMP expression may be regulated by DNA methylation. The purpose of the present investigation was to analyze the expression of MMP2 and MMP9 in periapical granulomas and radicular cysts and to test the hypothesis that, in these lesions, their transcription may be modulated by DNA methylation.
Methylation-specific polymerase chain reaction was used to evaluate the DNA methylation pattern of the MMP2 gene in 13 fresh periapical granuloma samples and 10 fresh radicular cyst samples. Restriction enzyme digestion was used to assess methylation of the MMP9 gene in 12 fresh periapical granuloma samples and 10 fresh radicular cyst samples. MMP2 and MMP9 messenger RNA transcript levels were measured by quantitative real-time polymerase chain reaction.
All periapical lesions and healthy mucosa samples showed partial methylation of the MMP2 gene; however, periapical granulomas showed higher MMP2 mRNA expression levels than healthy mucosa (P = .014). A higher unmethylated profile of the MMP9 gene was found in periapical granulomas and radicular cysts compared with healthy mucosa. In addition, higher MMP9 mRNA expression was observed in the periapical lesions compared with healthy tissues.
The present study suggests that the unmethylated status of the MMP9 gene in periapical lesions may explain the observed up-regulation of messenger RNA transcription in these lesions.
基质金属蛋白酶（MMPs）是负责降解细胞外基质成分的主要酶类，并参与根尖周炎性病变的发病机制。MMP的表达可能受DNA甲基化调控。本研究的目的是分析MMP2和MMP9在根尖周肉芽肿和根端囊肿中的表达，并验证在这些病变中其转录可能受DNA甲基化调节的假说。
采用甲基化特异性聚合酶链反应评估13份新鲜根尖周肉芽肿样本和10份新鲜根端囊肿样本中MMP2基因的DNA甲基化模式。采用限制性内切酶消化法评估12份新鲜根尖周肉芽肿样本和10份新鲜根端囊肿样本中MMP9基因的甲基化情况。通过定量实时聚合酶链反应测量MMP2和MMP9信使核糖核酸转录水平。
所有根尖周病变和健康黏膜样本均显示MMP2基因存在部分甲基化；然而，根尖周肉芽肿的MMP2信使核糖核酸表达水平高于健康黏膜（P = .014）。与健康黏膜相比，根尖周肉芽肿和根端囊肿中MMP9基因的未甲基化情况更为明显。此外，与健康组织相比，根尖周病变中观察到更高的MMP9信使核糖核酸表达。
本研究表明，根尖周病变中MMP9基因的未甲基化状态可能解释了这些病变中观察到的信使核糖核酸转录上调现象。
