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.     

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白细胞介素-1(interleukin-1,IL-1)是人体内非常活跃的促炎细胞因子,可刺激内皮细胞和白细胞释放一系列炎性介质,由此引发局部组织或全身的的炎症.牙周病是发生在牙龈、牙周膜和牙槽骨等牙齿支持组织的一种慢性破坏性疾病,其病理机制与牙周局部炎症有密切的联系.本文就IL-1的分化、功能及其与牙周病的关系做一综述.     

牙周健康状况与男性不育症相关性的研究进展

口腔健康与人体全身健康密切相关。牙周病是一种发生于牙周支持组织的口腔感染性疾病,与多种全身系统性疾病存在相关性。研究表明男性不育症与口腔疾病、特别是牙周病可能存在关联。然而,其作用机制尚未明确,目前存在两种假说,其一为牙周细菌慢性感染,其二为细胞因子的作用。本文主要就牙周疾病与男性不育症相关性及其可能作用机制进行综述。     

IL-23/IL-17炎性轴与牙周炎关系的研究进展

牙周病是以牙周致病菌为始发因素的一种造成牙周支持组织破坏的疾病,是导致牙齿丧失的主要原因。牙周组织的破坏一方面由细菌产生的各种破坏性酶、细菌的直接入侵及代谢产物等造成直接的破坏,另一方面,因牙周细菌引发的机体免疫,造成继发性的免疫破坏,而且目前观点认为,免疫性继发性破坏是牙周组织破坏的主要原因。本文对IL-23及IL-23/IL-17炎性轴在牙周病理性损伤中的作用进行了较为详细的阐述,可对牙周病的病理机制有更深入的理解,为今后牙周炎治疗提供科学的理论依据。     

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.     

一种很有前景的牙周新附着手术——引导牙周组织再生术

牙周病是一组以牙周支持组织破坏、牙齿松动脱落为特征的疾病。常规的牙周治疗如洁刮治,Widman翻瓣术后愈合往往是形成长结合上皮(Long Junctional Epithelium LJE),防碍了牙周组织的再生与附着。近年     

线粒体自噬在牙周炎发生发展过程中的研究进展

牙周炎是一种由菌斑生物膜引起牙周支持组织破坏的慢性炎症性疾病,主要以牙龈炎症和牙槽骨进行性破坏为特征。线粒体自噬是通过自噬选择性清除细胞内功能失调或受损的线粒体来调节细胞内稳态的主要机制,在线粒体质量和数量控制中发挥关键作用。近年来有研究发现：线粒体自噬可以通过抑制牙周炎症反应、降低细胞凋亡、促进牙周韧带干细胞成骨分化等多种途径参与牙周病的发生和发展,为牙周病的治疗提供了有前景的治疗靶点。本文就线粒体自噬的分子机制及其在牙周病发生发展中的作用等方面的研究进展作一综述。     

牙周膜干细胞的研究进展

牙周病是一种由菌斑微生物引起的慢性感染性疾病,可引起牙周支持组织的破坏和丧失,最终导致牙齿松动脱落。牙周病治疗的最终目标是修复和重建受损的牙周支持组织。从牙周膜中分离获取的间充质干细胞具有成体干细胞的特性及多重分化潜能,可以分化为骨组织和牙周支持组织等多种类型的组织,这对牙周组织修复再生和牙周组织工程具有重大意义,因而备受关注。本文就牙周膜干细胞、牙周膜干细胞的生物学特性、牙周膜干细胞的影响因素及其调控机制等研究进展作一综述。     

糖尿病患者口腔牙周状态观察

口腔内菌斑(细菌及其毒素)和牙石是牙周病病因和发展过程中的重要局部因素;但对牙周病患者的全身情况,如健康状况、系统性疾病与牙病的关系,了解得并不深入。诸如糖尿病与牙周病的关系,糖尿病患者的牙周病发病情况,牙周破坏严重程度、破坏速度等方面的研究资料都不尽完善。本     

牙周病活动期龈沟液标记物研究进展

牙周炎是发生于牙周支持组织的炎症性疾病,并导致了牙周连接组织的附着和牙槽骨的进行性破坏.其发展呈现活动期与静止期交替出现的特点.近些年来,国内外学者们都致力于与牙周炎活动期相关的标记物的研究,以期对牙周炎活动期进行准确的判断和预测.本文就牙周病活动期龈沟液中相关标记物研究进展做一综述.     

Bacterial invasion and persistence: critical events in the pathogenesis of periodontitis?

Periodontitis is chronic inflammation of the periodontium caused by the host's inflammatory response to plaque biofilm, which destroys tooth‐supporting soft and hard tissues. Periodontitis is a complex disease that involves interactions among three main features – microbial challenge, the host immune response, and environmental and genetic risk factors – in its pathogenesis. Although periodontitis has been regarded as the result of hyperimmune or hyperinflammatory responses to plaque bacteria, recent studies indicate that periodontal pathogens are rather poor activators and/or suppressors of the host immune response. This raises the question of how periodontal pathogens cause inflammation. To resolve this issue, in the present review we propose that bacterial invasion into gingival tissue is a key event in the initiation of periodontitis and that the persistence of these bacteria within host tissue results in chronic inflammation. In support of this hypothesis, we present the ways in which microbial, environmental and genetic risk factors contribute to bacterial invasion. It is hoped that the current model will instigate active discussion and new research to complete the puzzle of this complex disease process.     

Host-pathogen interactions in progressive chronic periodontitis

Periodontitis is an infection characterized by the occurrence of supporting tissue destruction with an episodic nature. Disease progression is often determined by the loss of attachment level or alveolar bone, and sequential probing of periodontal attachment remains the most commonly utilized method to diagnose progressive destruction of the periodontium. The tolerance method has been the most extensive clinical method used in recent years to determine site-specific attachment level changes. There is abundant evidence that major tissue destruction in periodontal lesions results from the recruitment of immune cells. Considerable effort has been made to study the host cell and mediator profiles involved in the pathogenesis of chronic periodontitis, but the definition of active sites, where current periodontal breakdown occurs, and consecutive characterization of the mediators involved are still among the main concerns. In the present review, we summarize periodontopathic bacteria and host factors, including infiltrating cell populations, cytokines, and host matrix metalloproteinases, associated with under-going episodic attachment loss that could partly explain the mechanisms involved in destruction of the supporting tissues of the tooth.     

B细胞骨免疫在牙周炎中的作用

牙槽骨吸收是牙周炎最为重要的病理特征,也是导致牙齿松动脱落、口腔功能异常的最主要原因。最新研究表明,宿主免疫是牙周炎过程中导致牙槽骨吸收的最主要因素。这一过程中所涉及的抗体、免疫细胞及炎症因子可引发局部成骨-破骨平衡紊乱,造成骨破坏。这种骨系统与免疫系统间的密切交互作用称为骨免疫。鉴于牙周炎宿主的主要免疫类型为适应性体液免疫,B细胞骨免疫在牙周炎发生发展过程中就显得尤为重要。因此,探索、揭示B细胞骨免疫,就成为深度解析牙周炎发生、发展与转归的有效途径。已有研究证实B细胞的发育过程伴随着骨密度或形态的改变,笔者回顾B细胞骨免疫在牙周炎病理进程中的作用相关研究表明,B细胞通过转录因子(如RANKL、PU.1、E2A等)调控骨细胞系的发育过程,此外,由B细胞所表达的多种细胞因子(如IFN-γ、IL-17、IL-10、TGF-β等)亦可参与骨系统细胞的调节。     

Odanacatib,A Cathepsin K‐Specific Inhibitor,Inhibits Inflammation and Bone Loss Caused by Periodontal Diseases

Background: Periodontitis is a bacteria‐induced inflammatory disease mainly affecting periodontal tissues, leading to periodontal inflammation, bone breakdown, and loss of the tooth. The main obstacle for treating periodontitis effectively is the difficulty in finding a target that can inhibit bone loss and inflammation simultaneously. Recent studies showed that cathepsin K (CTSK) might have functions in the immune system besides its role in osteoclasts. Thus, targeting CTSK would have a potential therapeutic effect in both the bone system and the immune system during the progression of periodontitis. Methods: In the current study, a small molecular inhibitor (odanacatib [ODN]) is explored to inhibit the function of CTSK in a bacteria‐induced periodontitis mouse model. Results: The application of ODN decreased the number of osteoclasts, macrophages, and T cells, as well as the expression of Toll‐like receptors (TLRs) in the periodontitis lesion area. Furthermore, lack of CTSK inhibited the expression of TLR4, TLR5, and TLR9 and their downstream cytokine signaling in the gingival epithelial cells in periodontitis lesions, demonstrating that the innate immune response was inhibited in periodontitis. Conclusion: The present results show that inhibition of CTSK can prevent bone loss and the immune response during the progression of periodontitis, indicating that CTSK is a promising target for treating inflammatory diseases such as periodontitis by affecting both osteoclasts and the immune system.     

Periodontitis is an inflammatory disease of oxidative stress: We should treat it that way

Periodontitis is a highly prevalent disease. As it progresses, it causes serious morbidity in the form of periodontal abscesses and tooth loss and, in the latter stages, pain. It is also now known that periodontitis is strongly associated with several nonoral diseases. Thus, patients with periodontitis are at greater risk for the development and/or exacerbation of diabetes, chronic obstructive pulmonary disease, and cardiovascular diseases, among other conditions. Although it is without question that specific groups of oral bacteria which populate dental plaque play a causative role in the development of periodontitis, it is now thought that once this disease has been triggered, other factors play an equal, and possibly more important, role in its progression, particularly in severe cases or in cases that prove difficult to treat. In this regard, we allude to the host response, specifically the notion that the host, once infected with oral periodontal pathogenic bacteria, will mount a defense response mediated largely through the innate immune system. The most abundant cell type of the innate immune system – polymorphonuclear neutrophils – can, when protecting the host from microbial invasion, mount a response that includes upregulation of proinflammatory cytokines, matrix metalloproteinases, and reactive oxygen species, all of which then contribute to the tissue damage and loss of teeth commonly associated with periodontitis. Of the mechanisms referred to here, we suggest that upregulation of reactive oxygen species might play one of the most important roles in the establishment and progression of periodontitis (as well as in other diseases of inflammation) through the development of oxidative stress. In this overview, we discuss both innate and epigenetic factors (eg, diabetes, smoking) that lead to the development of oxidative stress. This oxidative stress then provides an environment conducive to the destructive processes observed in periodontitis. Therefore, we shall describe some of the fundamental characteristics of oxidative stress and its effects on the periodontium, discuss the diseases and other factors that cause oxidative stress, and, finally, review potentially novel therapeutic approaches for the management (and possibly even the reversal) of periodontitis, which rely on the use of therapies, such as resveratrol and other antioxidants, that provide increased antioxidant activity in the host.     

The complement system and its role in the pathogenesis of periodontitis: current concepts

Periodontitis is a highly prevalent inflammatory disease in tooth supporting tissues, induced by bacteria growing in a biofilm on tooth surfaces. Components of the complement system are present in the periodontal tissue and the system is activated in periodontitis. Continuous complement activation and modulation by bacteria within the biofilm in periodontal pockets, however, may enhance local tissue destruction, providing the biofilm with both essential nutrients and space to grow. A more profound understanding of the mechanisms involved in complement‐derived tissue degradation may facilitate the development of new treatment concepts for periodontitis. Further studies on the role of complement in periodontitis pathogenesis may also contribute to the understanding of why some individuals fail to resolve periodontitis. Here, we review evidence that links complement to the pathogenesis of periodontitis with an emphasis on interaction of complement with bacteria from periodontitis‐associated biofilm.     

The role of vitamin D in periodontal health and disease

Vitamin D plays an essential role in calcium and bone metabolism, immune regulation and possesses profound anti-inflammatory effects. Evidence suggests that low serum vitamin D is associated with increased severity of periodontitis, a chronic inflammatory condition characterised by destruction of the supporting tissues surrounding the tooth, which has several shared risk factors with other chronic non-communicable diseases. The biological functions of vitamin D are mediated by its strong anti-microbial, anti-inflammatory, and host modulatory properties. Experimental periodontitis models involving targeted deletion of 1α-hydroxylase, the enzyme responsible for the conversion of inactive substrate to active 1,25(OH)₂D₃ (calcitriol), showed augmented alveolar bone loss and gingival inflammation. Vitamin D receptor (VDR) gene polymorphisms have also been associated with increased severity of periodontitis. Thus, the involvement of vitamin D in the pathogenesis of periodontitis is biological plausible. Clinical studies have consistently demonstrated an inverse relationship between serum 25OHD₃ and periodontal disease inflammation. However, due to the paucity of well-designed longitudinal studies, there is less support for the impact of vitamin D status on periodontal disease progression and tooth loss. The evidence emphasises the importance of maintaining vitamin D sufficiency in supporting periodontal health. This review aims to first examine the biological mechanisms by which vitamin D might influence the pathogenesis of periodontal disease and second, discuss the clinical evidence which implicate the role of vitamin D in periodontal disease.     

Periodontal herpesviruses: prevalence,pathogenicity, systemic risk

Periodontitis is an infectious/inflammatory disease characterized by the loss of periodontal ligament and alveolar bone. Herpesviruses are frequent inhabitants of periodontitis lesions, and the periodontopathogenicity of these viruses is the topic of this review. In 26 recent studies from 15 countries, subgingival cytomegalovirus, Epstein–Barr virus and herpes simplex virus type 1, respectively, yielded median prevalences of 49%, 45% and 63% in aggressive periodontitis, 40%, 32% and 45% in chronic periodontitis, and 3%, 7% and 12% in healthy periodontium. An active herpesvirus infection of the periodontium exhibits site specificity, is a potent stimulant of cellular immunity, may cause upgrowth of periodontopathic bacteria and tends to be related to disease‐active periodontitis. Pro‐inflammatory cytokines induced by the herpesvirus infection may activate matrix metalloproteinases and osteoclasts, leading to breakdown of the tooth‐supportive tissues. The notion that a co‐infection of herpesviruses and specific bacteria causes periodontitis provides a plausible etiopathogenic explanation for the disease. Moreover, herpesvirus virions from periodontal sites may dislodge into saliva or enter the systemic circulation and cause diseases beyond the periodontium. Periodontal treatment can diminish significantly the periodontal load of herpesviruses, which may lower the incidence and magnitude of herpesvirus dissemination within and between individuals, and subsequently the risk of acquiring a variety of medical diseases. Novel and more effective approaches to the prevention and treatment of periodontitis and related diseases may depend on a better understanding of the herpesvirus–bacteria–immune response axis.     

C-reactive protein as a marker of periodontal disease

Periodontal subgingival pathogens affect local and systemic immune and inflammatory response and cause the release of cytokines; this results in periodontal destruction and initiation of an acute phase systemic inflammatory response characterized by the release of C-reactive proteins (CRP). This study set out to evaluate the serum concentration of CRP that can be used as a marker of periodontal disease as well as a risk indicator for cardiovascular disease. Based on their periodontal status, 45 patients were divided into three groups. The following clinical parameters were recorded: plaque index, gingival index, bleeding index, probing pocket depth, and clinical attachment levels. Scoring was done on six tooth surfaces for all teeth. For the CRP assessment, blood samples were collected from subjects at the time of clinical examination. The results indicated an increase in serum CRP levels in patients with generalized aggressive periodontitis and chronic periodontitis as compared to controls.