口腔鳞状细胞癌的表观遗传学研究现状和进展

口腔鳞状细胞癌(OSCC)是最常见的口腔颌面部恶性肿瘤之一,但目前对于OSCC的具体发病机制并不十分清楚。当前的研究认为在OSCC发生发展中的基因变化因素主要包括基因突变与表观遗传修饰异常。表观遗传修饰是可遗传、可逆转的生物学行为,主要包括DNA甲基化、组蛋白修饰、非编码RNA调控等。近来研究发现,表观遗传修饰的改变尤其是DNA甲基化对OSCC的发病过程意义重大。对于表观遗传学修饰改变的进一步探索将有助于我们理解OSCC的发病机制,该机制将为OSCC的诊断、治疗、预后提供一个新的研究思路,并且为新型抗肿瘤药物的研发工作,提供了新的理论基础。     

表观修饰对间充质干细胞功能调控的研究进展

间充质干细胞(Mesenchymal stem cells,MSCs)是成体干细胞的一种,由于其自我更新、多向分化、靶向迁移、免疫调控、抗瘢痕以及抗凋亡等诸多重要的生理功能,使其在组织修复和再生方面被寄予厚望,然而这些功能的详细机理仍不明了。表观遗传学是研究在无细胞核DNA序列改变的情况时,基因功能的可逆的、可遗传的改变,主要包括DNA甲基化,组蛋白修饰,非编码RNA调控,基因组印记等。通过调控基因的转录过程,表观调控在MSCs的各项生理功能中均起着重要作用。本文总结了近年来表观调控对MSCs的分化能力,迁移能力和免疫调控功能等方面的影响的研究进展作一综述。     

表观遗传学及其调控与牙周病

表观遗传学是指不涉及DNA序列改变,而是通过有丝分裂和减数分裂进行遗传的基因表达变化的遗传学分支学科,其调控机制主要包括DNA甲基化、组蛋白修饰、染色质重塑和非编码RNA调控等.牙周炎病因复杂,且被吸收、破坏的牙槽骨很难实现功能性再生.表观遗传学在导致炎症的发生及促进骨再生的过程中扮演着重要角色,从表观遗传学及其调控的角度来预防牙周病的发生,促进牙槽骨的功能性再生,将是未来重要的研究内容,具有重要的临床意义.     

表观遗传在牙发育中的作用

表观遗传是指DNA序列不发生变化,基因的表达方式发生了可遗传改变的一种遗传方式,主要包括DNA甲基化、组蛋白修饰和非编码RNA调控等。在牙发育过程中,传统基因调控与表观遗传学调控共同参与协同,调节细胞增殖分化相关基因的时空表达。探索牙发育过程中的表观遗传调控机制,可为牙再生提供线索和思路,本文主要对表观遗传调控在牙发育...     

牙周膜干细胞表观遗传学研究进展

牙周膜干细胞(periodontal ligament stem cells,PDLSCs)是牙周膜组织中的间充质干细胞,是牙周组织再生和修复的重要细胞群,牙周微环境的变化会影响牙周膜干细胞的生物学特性.表观遗传(epigenetics)是指不基于DNA序列的变化,而出现稳定可遗传的基因表达水平及功能的改变.环境因素是影响表观遗传的重要因素之一,暴露环境的不同可以引起表观修饰改变,进而影响基因表达.表观遗传是干细胞生物学特性的重要内源性调控机制,在干细胞中的变化稳定可遗传,并具有可逆性.近年来牙周膜干细胞的表观遗传调控已成为研究热点,本文通过对表观遗传调控对牙周膜干细胞生物学特性的影响进行综述,以期使牙周膜干细胞更好地应用于牙周再生修复.     

牙根发育中的表观遗传学研究进展

牙根发育开始于牙冠发育完成后,涉及细胞增殖、分化、迁移、凋亡等诸多细胞生物学过程。表观遗传调控通过组蛋白修饰、DNA甲基化、非编码RNA调控等方式靶向调节基因表达。来自遗传小鼠模型和体外研究结果显示,这些靶向调节基因包括上皮-间质相互作用信号分子、关键细胞周期蛋白、成牙本质细胞分化及成熟的关键转录因子和功能分子等。利用遗传修饰小鼠模型结合单细胞组学等新兴生物学技术,将有助于进一步发现和阐明牙根发育的表观遗传学机制。     

口腔微生物致宿主表观遗传改变的研究进展

微生物在感染宿主的过程中能够调控宿主的生理功能,其中一种重要的调控方式是表观遗传调控.表观遗传是指在基因DNA序列不发生改变的情况下,基因的表达和功能发生稳定改变,并产生可遗传的表型.表观遗传调控在微生物引起宿主免疫反应的过程中起到重要作用.明确微生物对宿主的表观遗传调控机制有利于开展临床靶向治疗,加强表观遗传调节剂的...     

牙周病与肺部炎症相关性的动物实验研究

目的 建立肺部炎症、牙周病及两者相互叠加的实验动物模型,探讨两者的相互关系.方法 30只昆明小鼠随机分两组,选取15只(A组)通过石膏粉鼓吹法建立肺部炎症的动物模型,建模后将A组小鼠随机分为3个亚组,通过钢丝结扎+高糖饮食3周、5周,叠加建立肺部炎症+牙周病模型:A1组(肺部炎症+牙周正常组)、A2组(肺部炎症+轻度牙周病组)、A3组(肺部炎症+重度牙周病组).另15只(B组)同期正常饲养,通过与A组相同的方法 建立牙周病模型,为B1组(空白对照组)、B2组(轻度牙周病组)、B3组(重度牙周病组).结果 A组:肺组织的病理切片炎症程度A3组＞A2组＞A1组,肺灌洗液淋巴细胞百分比计数A3组＞A2组＞A1组(P＜0.05).牙周组织的炎症程度A3组＞A2组＞A1组(P＜0.05).B组:肺组织的病理切片炎症程度B3组＞B2组＞B1组,肺灌洗液淋巴细胞百分比计数B3组＞B2组＞B1组(P＜0.05).牙周组织的炎症程度B3组＞B2组＞B1组(P＜0.05).结论 石膏粉鼓吹加钢丝结扎+高糖饮食可建立小鼠肺部炎症及牙周病叠加模型.牙周感染可加重或引发肺部炎症,且牙周病越严重其合并或引发的肺部炎症越严重,但肺部炎症在短时间内不会引发或加重牙周感染.     

Expression of TET2 enzyme indicates enhanced epigenetic modification of cells in periodontitis

DNA methylation is an important epigenetic mechanism involved in the regulation of gene expression, and a reduction in DNA methylation influences cell‐cycle progression and cell differentiation in inflammatory cells. The aim of the present study was to analyze the DNA‐methylation pattern at local and global/systemic levels in patients with periodontitis and gingivitis. Twenty‐one subjects with generalized, severe periodontitis and 17 subjects with gingival inflammation but no attachment loss were recruited. Gingival biopsies and peripheral blood samples were collected and prepared for immunohistochemical analysis of 5‐methylcytosine (5mC), 5‐hydroxymethylcytosine (5hmC), ten‐eleven translocation 2 (TET2), and DNA methyltransferase 1 (DNMT1). Whilst a similar pattern for 5mC and 5hmC DNA methylation was found in both types of lesions, a significantly larger proportion of TET2‐positive cells was found in periodontitis lesions than in gingivitis lesions. Quantitative real‐time PCR analysis showed no differences between gingivitis and periodontitis lesions regarding expression of TET2 and isocitrate dehydrogenase (IDH) genes, while the global level of 5hmC was significantly higher in blood than in tissue in patients with periodontitis. It is suggested that epigenetic changes are more common in periodontitis lesions than in gingivitis lesions and that such changes are tissue specific.     

Association between periodontal disease and non-fatal ischemic stroke: a case-control study

Objective. This study aimed to investigate the association between clinical and radiological markers of periodontal disease and ischemic stroke and to assess the potential influence of inflammatory response on the observed associations. Methods. A prospective case-control study including a series of 48 cases with a minor ischemic stroke and 47 controls was conducted at the University Hospital of Dijon. Vascular risk factors, clinical dental examination (plaque index, gingival index, percentage of pockets >5 mm, percentage of bleeding on probing (BOP) sites), dental panoramic (bone loss) and biological parameters (CRP, total cholesterol, HDL, LDL, fasting glucose) were collected. Conditional regression analyses were performed to identify factors associated with ischemic stroke. Results. The prevalence of hypertension, high CRP and glucose levels and overall odontological variables was higher in stroke patients. In multivariable analyses, hypertension (OR = 12.56; 95% CI = 2.29–69.96, p = 0.004), CRP levels >5 mg/L (OR = 18.54; 95% CI = 2.01–171.17, p = 0.010), BOP (OR = 1.049; 95% CI = 1.012–1.88, p = 0.009) and bone loss >20% (OR = 1.053; 95% CI = 1.017–1.091, p = 0.004) were associated with ischemic stroke. Among stroke patients, there was a non-significant trend towards higher CRP levels in patients with bone loss >20% compared with those with bone loss <20% (8.1 ± 1.27 mg/L vs 3.12 ± 3.14 mg/L, p = 0.25), whereas other biological parameters were very similar between the two groups. Conclusion. This case-control study demonstrates that periodontal disease, especially markers such as BOP and bone loss, is independently associated with ischemic stroke.     

DNA methylation status of the IL8 gene promoter in oral cells of smokers and non-smokers with chronic periodontitis

Aim: This study analysed the status of DNA methylation in the promoter region of the IL8 gene in oral mucosa cells from healthy, smoker and non-smoker subjects with chronic periodontitis and compared these findings among groups with mRNA levels.
Material and Methods: Genomic DNA from epithelial oral cells of 41 healthy subjects, 30 smokers with chronic periodontitis and 40 non-smokers with chronic periodontitis were purified and modified by sodium bisulphite. Genomic DNA from blood leucocytes and gingival cells from biopsies of 13 subjects of each group were also purified and modified by sodium bisulphite. Modified DNA was submitted by methylation-specific polymerase chain reaction (PCR) (MSP), electrophoresed on 10% polyacrylamide gels and stained with SYBR Gold. Total RNA from gingival cells was also isolated using the TRIzol reagent, and real-time PCR performance was used to detect the levels of interleukin-8 mRNA.
Results: Our results indicate that individuals with chronic periodontitis, independent of smoking habit, have a higher percentage of hipomethylation of the IL8 gene than those controls in epithelial oral cells ( p <0.0001), and expression of higher levels of interleukin-8 (IL-8) mRNA than controls in gingival cells ( p= 0.007). No significant differences among groups were observed in gingival cells and blood cells.
Conclusion: We conclude that inflammation in the oral mucosa might lead to changes in the DNA methylation status of the IL8 gene in epithelial oral cells.     

Association between bacteriophage-infected Actinobacillus action-mycetemcomitans and rapid periodontal destruction

Actinobacillus actinomycetemcomitans was isolated from periodontal pockets in a patient suffering from prepubertal periodontitis. Electron microscopy revealed 3 different groups of bacteriophages in filtrates of subgingival plaque from all the active periodontal lesions. Phage infected A. actinomycetemcomitans in this patient was restricted to periodontal pockets which, according to standardized roentgenograms, had shown bone destruction during the past 12 months. A follow-up study of 7 months revealed that a "burned out" site which harbored noninfected A. actinomycetemcomitans, turned into an active site at the same time as the A. actinomycetemcomitans of that site became infected with the phages. These findings indicate a relationship between rapid prepubertal periodontal destruction and phage-infected A. actinomycetemcomitans.     

The use of rodent models to investigate host-bacteria interactions related to periodontal diseases

Even though animal models have limitations, they are often superior to in vitro or clinical studies in addressing mechanistic questions and serve as an essential link between hypotheses and human patients. Periodontal disease can be viewed as a process that involves four major stages: bacterial colonization, invasion, induction of a destructive host response in connective tissue and a repair process that reduces the extent of tissue breakdown. Animal studies should be evaluated in terms of their capacity to test specific hypotheses rather than their fidelity to all aspects of periodontal disease initiation and progression. Thus, each of the models described below can be adapted to test discrete components of these four major steps, but not all of them. This review describes five different animal models that are appropriate for examining components of host-bacteria interactions that can lead to breakdown of hard and soft connective tissue or conditions that limit its repair as follows: the mouse calvarial model, murine oral gavage models with or without adoptive transfer of human lymphocytes, rat ligature model and rat Aggregatibacter actinomycetemcomitans feeding model.     

Association between metabolic syndrome and periodontal disease

Background: Metabolic syndrome has been suggested as a potential risk factor for periodontal disease. Data based on NHANES III, with 7431 subjects aged 20 years or older, were analysed to confirm the association between metabolic syndrome and periodontal disease, and identify which components of metabolic syndrome might play a role in this association. Methods: Clinical criteria for metabolic syndrome included: (1) abdominal obesity; (2) increased triglycerides; (3) decreased HDL cholesterol; (4) hypertension or current use of hypertension medication; and (5) high fasting plasma glucose. Periodontal disease was evaluated by probing pocket depth (PPD) and was defined as mean PPD ≥2.5 mm. Results: Women with two or more metabolic components had significantly increased odds of having periodontal disease as compared to those with no component [(two components, OR = 5.6 (95% CI: 2.2–14.4); three or more, OR = 4.7 (2.0–11.2)]. Using the definition of metabolic syndrome as having three to five metabolic components (reference group with <3 components), the adjusted odds ratios were 1.0 (0.7–1.6) for men and 2.1 (1.2–3.7) for women. Abdominal obesity was the largest contributory factor in both genders. Conclusions: While the association between metabolic syndrome and periodontal disease was particularly significant for women, abdominal obesity appeared to be the contributing metabolic factor for both genders.     

The relationship between periodontal diseases and diabetes: an overview

Diabetes mellitus, caused by the malfunction of insulin-dependent glucose and lipid metabolism, presents with the classical triad of symptoms: polydypsia, polyuria, and polyphagia which are often accompanied by chronic fatigue and loss of weight. Complications of diabetes mellitus include retinopathy, nephropathy, neuropathy, and cardiovascular disease. Periodontal diseases are infections affecting the periodontium and resulting in the loss of tooth support. The association between diabetes mellitus and periodontitis has long been discussed with conflicting conclusions. Both of these diseases have a relatively high incidence in the general population (diabetes 1% to 6% and periodontitis 14%) as well as a number of common pathways in their pathogenesis (both diseases are polygenic disorders with some degree of immunoregulatory dysfunction). On the one hand, numerous reports indicate a higher incidence of periodontitis in diabetics compared to healthy controls, while other reports fail to show such a relationship. Clarification of this dilemma is occurring as the diagnostic criteria for periodontitis and diabetes mellitus improve, controlled studies with increased sample sizes are carried out, and the studies take into account major confounding variables that impact on the pathogenesis of both diseases. Current studies tend to support a higher incidence and severity of periodontitis in patients with diabetes mellitus. The overview looks at the bidirectional relationship between periodontitis and diabetes. An analysis of the National Health and Nutrition Examination Survey (NHANES) III data set confirms the previously reported significantly higher prevalence of periodontitis in diabetics than in non-diabetics (17.3% versus 9%). The analysis of the data also shows that the prevalence of diabetes in patients with periodontitis is double that seen in the non-periodontitis patients (12.5% versus 6.3%) and that this difference is also statistically significant. The pathogenesis of the 2 diseases is reviewed with an emphasis on common genetic and immune mechanisms. On the basis of the overview, 2 hypotheses for testing the relationship between periodontitis and diabetes are discussed. The first proposes a direct causal or modifying relationship in which the hyperglycemia and hyperlipidemia of diabetes result in metabolic alterations that may then exacerbate bacteria-induced inflammatory periodontitis. The second hypothesis proposes that a fortuitous combination of genes (gene sets) could result in a host who, under the influence of a variety of environmental stressors, could develop either periodontitis or diabetes or both.     

Association between volatile sulfur compounds and periodontal disease progression in elderly non-smokers

Background: Periodontal pathogenic microorganisms produce volatile sulfur compounds (VSCs), such as hydrogen sulfide, methyl mercaptan, and dimethyl sulfide. VSCs are toxic to periodontal tissue. Therefore, there is a relationship between periodontitis and the VSC level of mouth air. However, the association between VSC and periodontal disease progression has not been investigated in a longitudinal study. The purpose of this study is to evaluate the association between VSCs in mouth air and periodontal disease progression among elderly dentulous non‐smokers. Methods: Two hundred forty‐one dentulous non‐smokers (103 males and 138 females; all 70 years old) had their VSC levels examined with a portable sulfide monitor, and their periodontal status was assessed. Periodontal examinations were performed at baseline and once a year for 3 years to investigate the clinical attachment levels of all teeth. Participants were classified by membership in tertile groups (lowest, middle, and highest) according to the value of baseline VSC measurements. Results: In negative binomial regression analysis, the number of teeth with periodontal disease progression for participants in the highest tertile of VSC measurement was greater (incidence rate ratio of 1.33, P = 0.011) than for the reference group (lowest tertile of VSC measurement) after simultaneously adjusting for sex, number of remaining teeth, and maximum clinical attachment level. Conclusions: VSC measurements were significantly associated with periodontal disease progression in a non‐smoking dentulous elderly population. This suggests that VSC measurements are useful for the diagnosis of periodontal disease progression.