Center for Oral Health Research, College of Dentistry, University of Kentucky, 1095 VA Drive, HSRB 414, Lexington, KY 40536-0305, USA.
Apoptosis. 2013 Mar;18(3):249-59. doi: 10.1007/s10495-013-0806-x.
Apoptotic processes are important for physiologic renewal of an intact epithelial barrier and contribute some antimicrobial resistance for bacteria and viruses, as well as anti-inflammatory effects that benefits the mucosa. The oral cavity presents a model of host-bacterial interactions at mucosal surfaces, in which a panoply of microorganisms colonizes various niches in the oral cavity and creates complex multispecies biofilms that challenge the gingival tissues. This report details gene expression in apoptotic pathways that occur in oral mucosal tissues across the lifespan, using a nonhuman primate model. Macaca mulatta primates from 2 to 23 years of age (n = 23) were used in a cross-sectional study to obtain clinical healthy gingival tissues specimens. Further, mRNA was prepared and evaluated using the Affymetrix Rhesus GeneChip and 88 apoptotic pathway genes were evaluated. The results identified significant positive correlations with age in 12 genes and negative correlations with an additional five genes. The gene effects were predicted to alter apoptosis receptor levels, extrinsic apoptotic pathways through caspases, cytokine effects on apoptotic events, Ca(+2)-induced death signaling, cell cycle checkpoints, and potential effects of survival factors. Both the positively and negatively correlated genes within the apoptotic pathways provided evidence that healthy tissues in aging animals exhibit decreased apoptotic potential compared to younger animals. The results suggested that decreased physiologic apoptotic process in the dynamic septic environment of the oral mucosal tissues could increase the risk of aging tissues to undergo destructive disease processes through dysregulated inflammatory responses to the oral microbial burden.
凋亡过程对于完整上皮屏障的生理更新很重要,并且为细菌和病毒提供了一些抗微生物的抗性,以及抗炎作用,从而有益于粘膜。口腔是粘膜表面宿主-细菌相互作用的模型,其中大量微生物定植于口腔的各个部位,并形成复杂的多物种生物膜,对牙龈组织构成挑战。本报告详细介绍了在整个生命过程中口腔粘膜组织中凋亡途径的基因表达情况,使用了非人类灵长类动物模型。从 2 到 23 岁(n = 23)的恒河猴灵长类动物用于横断面研究,以获得临床健康的牙龈组织标本。此外,使用 Affymetrix Rhesus GeneChip 制备并评估了 mRNA,并评估了 88 个凋亡途径基因。结果在 12 个基因中发现与年龄呈显著正相关,在另外 5 个基因中与年龄呈负相关。基因效应预计会改变凋亡受体水平、通过半胱天冬酶的外在凋亡途径、细胞凋亡事件的细胞因子效应、Ca(+2)-诱导的死亡信号、细胞周期检查点以及生存因子的潜在效应。凋亡途径中呈正相关和负相关的基因都表明,与年轻动物相比,衰老动物的健康组织表现出凋亡潜力降低。研究结果表明,口腔粘膜组织中动态感染环境中生理凋亡过程的减少可能会增加衰老组织发生破坏性疾病过程的风险,因为对口腔微生物负担的炎症反应失调。