PMS College of Dental Sciences and Research, Thiruvananthapuram, Kerala 695028 India.
Government Dental College, Thiruvananthapuram, Kerala 695011, India; PMS College of Dental Sciences and Research, Thiruvananthapuram, Kerala 695028 India.
Arch Oral Biol. 2017 Oct;82:19-26. doi: 10.1016/j.archoralbio.2017.05.010. Epub 2017 May 20.
Pathogens and host mediators can activate transcription factors in periodontal cells to bring about gene level alterations, thereby accentuating the periodontal disease process. Nuclear factor-kappa B (NF-κB) and signal transducers and activators of transcription 3 (STAT3) are two pivotal transcription factors implicated in chronic inflammatory diseases. But their importance in periodontal pathogenesis has not been investigated in detail. The aim of the present study was to evaluate the expression of activated transcription factors and their target genes in healthy and diseased periodontium.
Primary culture of periodontal ligament fibroblasts (PDLF) were established from healthy and diseased periodontium using explant culture methods. NF-κB and STAT3 activation in these cells by Porphyromonas gingivalis LPS (lipopolysaccharide) was demonstrated using confocal microscopy and mRNA expression of target genes were evaluated by quantitative real time PCR. NF-κB and STAT3 expression in diseased and healthy gingival tissues were analyzed using immunohistochemistry.
A basal upregulation of transcription factors and their target genes were noted in diseased PDLF compared to healthy ones. LPS challenge induced differential expression of NF-κB and STAT3 and their target genes in diseased PDLF compared to healthy ones. Immunohistochemical analysis revealed significant activation of transcription factors in diseased gingival tissues.
The findings of the present study reveal the role of transcription factors NF-κB and STAT3 in periodontal pathogenesis and disease susceptibility of fibroblast subpopulations in periodontal disease could be mediated through activation of NF-κB and STAT3. Since genetic factors are nonmodifyable, transcription factors are promising targets for future host modulation therapy.
病原体和宿主介质可激活牙周细胞中的转录因子，导致基因水平的改变，从而加重牙周病进程。核因子-κB（NF-κB）和信号转导和转录激活因子 3（STAT3）是两种与慢性炎症性疾病相关的关键转录因子。但它们在牙周病发病机制中的重要性尚未得到详细研究。本研究旨在评估健康和患病牙周组织中激活转录因子及其靶基因的表达。
采用组织块培养法从健康和患病牙周组织中建立牙周韧带成纤维细胞（PDLF）的原代培养。通过共聚焦显微镜观察牙龈卟啉单胞菌 LPS（脂多糖）对这些细胞中 NF-κB 和 STAT3 的激活，并通过定量实时 PCR 评估靶基因的 mRNA 表达。采用免疫组织化学分析检测疾病和健康牙龈组织中 NF-κB 和 STAT3 的表达。
与健康 PDLF 相比，患病 PDLF 中观察到转录因子及其靶基因的基础上调。LPS 刺激诱导患病 PDLF 中 NF-κB 和 STAT3 及其靶基因的差异表达，与健康 PDLF 相比。免疫组织化学分析显示转录因子在患病牙龈组织中明显激活。
本研究的结果揭示了转录因子 NF-κB 和 STAT3 在牙周病发病机制中的作用，并且牙周病中纤维母细胞亚群的疾病易感性可能通过 NF-κB 和 STAT3 的激活来介导。由于遗传因素是不可改变的，转录因子是未来宿主调节治疗的有前途的靶点。
