间充质干细胞源性外泌体在创面修复中的研究进展

外泌体是由细胞通过旁分泌途径产生的一种直径在30～100 nm的囊泡结构。作为活细胞分泌的一种亚细胞成分,外泌体广泛参与细胞间的信息交流。多项研究表明,间充质干细胞源性外泌体调控创面修复的多个过程。它可以通过抑制创面过度炎症反应,促进创面血管新生,促进成纤维细胞增殖、迁移,以及抑制创面瘢痕形成来促进创面的修复与再生。本文就间充质干细胞源性外泌体在创面修复中的作用及相关机制进行综述,为外泌体在临床中的应用提供依据。     

外泌体对M2型巨噬细胞的调控及其在心血管疾病中的作用①

外泌体是一种脂质微囊泡,可携带多种脂质、蛋白质、核酸,参与细胞间通讯,是心血管疾病的新型标志物和潜在治疗靶点。M2型巨噬细胞可抑制血管炎症反应、促进组织修复,在心血管疾病中发挥保护作用,其功能受多种因素调控。外泌体是近年逐渐受到关注的细胞对话新方式。本文根据外泌体来源进行分类,总结外泌体内不同物质对M2型巨噬细胞的调节作用、相关信号通路及其与心血管疾病的潜在关系。     

微小RNA在力相关牙周炎症反应和组织改建中的作用

微小核糖核酸(micro-ribonucleic acid,miRNA)是一种非编码单链RNA分子,可通过抑制靶基因mRNA的翻译来调控生物体遗传信息表达,参与体内多种生物学过程的发生发展。miRNA在机械力诱导机体产生的炎症性疾病和组织改建中发挥着重要作用。牙周组织中机械力敏感细胞可在力作用下导致牙周组织炎症反应、组织改建等病理/生理性变化,在这一过程中miRNA可能通过抑制这些细胞中特定基因的翻译,对力相关牙周炎症和组织改建的发生发展起到重要的调控作用。对miRNA在力相关炎症反应和组织改建,尤其是牙周炎症反应和组织改建中的作用展开综述。     

外泌体在周围神经损伤进程中的效应

背景:外泌体由于具有细胞间的通讯功能以及多种生物学特性,可以通过多种途径来干预疾病的发生发展,在周围神经损伤疾病治疗中具有巨大潜力。目的:综述外泌体在治疗周围神经损伤进程中的相关作用与作用机制,为临床治疗周围神经损伤以及基础研究提供一定的理论依据。方法:检索CNKI、PubMed等数据库建库至2019年10月期间关于外泌体与神经系统损伤相关的文献,检索词为“外泌体,周围神经损伤,miRNA,许旺细胞,炎症,血管再生”和“exosome,peripheral nervous injury,miRNA,schwann cell,inflammation,vessel regeneration”,共纳入60篇文献进行分析。结果与结论:①总结外泌体的结构与功能,发现其作为多种疾病的诊断指标与治疗方案具有很大的优势;②外泌体及其包含的miRNA、mRNA和蛋白质不但可以反映来源细胞的病理生理状态,而且被证实是重要的细胞间通讯及生物活性物质转运的重要方式;③从治疗周围神经损伤的途径(轴突再生、调节炎症、血管再生)方面,发现外泌体有助于周围神经损伤修复。     

炎症体及相关蛋白在力诱导牙周炎症反应中的作用

炎症体是一种多蛋白复合体,能介导IL-1β等多种炎症细胞因子释放,在炎症的发生发展中具有重要的作用。随着对炎症体研究的不断深入,目前已有文献报道炎症体可能参与机械力所诱导的机体炎症性疾病。与此同时,近年来研究显示,机械力可诱导牙周组织发生炎症反应,并伴随IL-1β和caspase-1/-5的表达。然而,炎症体及相关蛋白在力诱导牙周炎症反应中的作用尚不明确。综述炎症体的特点、在力相关炎症性疾病中的作用、机械力诱导的牙周炎症及其与炎症体和相关蛋白关系的研究进展。     

外泌体在免疫抑制性肿瘤微环境形成中的作用

外泌体(exosome)是细胞内多胞体与质膜融合后分泌到细胞外环境中的一种膜性囊泡。Exosome来源于晚期内体,是活细胞分泌而来,几乎所有的细胞都能分泌,广泛存在于各种体液中。Exosome参与细胞重要生理功能的调控,在免疫应答、凋亡、血管生成、炎症反应及肿瘤发生发展等过程中均有作用。Exosome可以作为多种疾病的早期诊断标志物,也能作为靶向药物的载体对疾病进行治疗。Exosome来源多样、成分复杂,既可以活化免疫系统,也可以促进免疫耐受。Exosome作为囊泡的一种,exosome在调节性T细胞、髓源性抑制细胞和肿瘤相关巨噬细胞等细胞的扩增方面具有重要作用,在免疫抑制性肿瘤微环境形成中发挥重要作用。现就exosome的生物学特性、免疫调节作用及其在免疫抑制性肿瘤微环境形成过程中的作用进行综述。     

肿瘤外泌体对免疫细胞的作用

外泌体是细胞主动分泌的双层囊泡小体,广泛存在于各种体液中,直径通常为30～100 nm。外泌体能将其携带的的脂类、蛋白质、核酸等多种重要的生物功能分子运输到受体细胞中,起到物质传递与信息交流的作用。肿瘤来源外泌体(tumor-derived exosomes,TEXs)与肿瘤的发生发展密切相关,既可作为抗原引发抗肿瘤免疫,更重要的是,也可负向调控多种免疫细胞功能,帮助肿瘤细胞免疫逃逸。本文主要对外泌体在多种肿瘤中对各类免疫细胞的调控作用进行分析总结。     

CD4+CD25+ Treg 细胞分泌外泌体在疾病中作用的研究进展

调节性T 细胞为T 细胞的一类控制体内自身免疫反应性的T 细胞亚群,在维持机体的免疫耐受以及调控免 疫应答中起重要作用。外泌体是细胞分泌的异质性纳米级胞外囊泡。现在研究认为外泌体在细胞间通讯中发挥重要作用, 外泌体可将其细胞内的多种RNA、DNA 片段、脂质和蛋白质等物质转送到不同的受体细胞,从而改变受体细胞的生物学活性。 多项研究证据表明Treg 细胞可分泌外泌体发挥免疫调节作用,并参与感染免疫、器官移植、超敏反应、自身免疫病以及肿瘤的 发生与发展。本文对Treg 细胞来源外泌体的组成成分、形成途径以及其免疫调节作用等进行综述。     

机械力刺激诱导机体组织炎症反应机制研究进展

机械力刺激能够诱发机体中包括牙周组织在内的多种组织发生无菌性炎症反应,并能促进免疫细胞以及一些非免疫细胞如牙周膜细胞发生焦亡(pyroptosis)。现有研究表明,Gasdermin-D(GSDMD)在炎症反应、细胞焦亡发生中具有重要作用,但GSDMD是否参与机械力刺激引发的炎症反应和细胞焦亡尚未可知。综述机械力刺激诱导机体组织炎症反应以及焦亡的信号通路研究进展。     

Inflammation in periodontal tissues in response to mechanical forces

Orthodontic forces are known to produce mechanical damage and inflammatory reactions in the periodontium and dental pulp, as well as inflammatory mediators, e.g. prostaglandins, interleukin (IL)-1, IL-6, tumor necrosis factor alpha, and receptor activator of nuclear factor kappaB ligand, in the periodontal ligament (PDL) and dental pulp. We have studied the effects of aging on the production of inflammatory mediators in the PDL using in vitro and in vitro methods and found that aging of PDL tissues may be an important factor in the severity of periodontal disease through a higher production of inflammatory mediators in response to mechanical forces. Further, the levels of inflammatory mediators in gingival crevicular fluid, an osmotically mediated inflammatory exudates found in the gingival sulcus, have been shown to be significantly elevated during orthodontic treatment. In order to reduce inflammation, low-level laser therapy has been recently studied in vitro and in vitro by many investigators as a substitute for anti-inflammatory drugs. Clinical and experimental studies have shown that low-level laser irradiation reduces orthodontic post-adjustment inflammation. We believe that orthodontic forces (mechanical forces) may play an important role in periodontal inflammation and that low-level laser therapy may be useful for its inhibition.     

Acetylcholine and the alpha 7 nicotinic receptor: a potential therapeutic target for the treatment of periodontal disease?

Objectives

The aim of this review is to examine the evidence for a functional cholinergic system operating within the periodontium and determine the evidence for its role in periodontal immunity.

Introduction

Acetylcholine can influence the immune system via the ‘cholinergic anti-inflammatory pathway’. This pathway is mediated by the vagus nerve which releases acetylcholine to interact with the α7 subunit of the nicotinic acetylcholine receptor (α7nAChR) on proximate immuno-regulatory cells. Activation of the α7nAChR on these cells leads to down-regulated expression of pro-inflammatory mediators and thus regulates localised inflammatory responses. The role of the vagus nerve in periodontal pathophysiology is currently unknown. However, non-neuronal cells can also release acetylcholine and express the α7nAChR; these include keratinocytes, fibroblasts, T cells, B cells and macrophages. Therefore, by both autocrine and paracrine methods non-neuronal acetylcholine can also be hypothesised to modulate the localised immune response.

Methods

A Pubmed database search was performed for studies providing evidence for a functional cholinergic system operating in the periodontium. In addition, literature on the role of the ‘cholinergic anti-inflammatory pathway’ in modulating the immune response was extrapolated to hypothesise that similar mechanisms of immune regulation occur within the periodontium.

Conclusion

The evidence suggests a functional non-neuronal ‘cholinergic anti-inflammatory pathway’ may operate in the periodontium and that this may be targeted therapeutically to treat periodontal disease.     

Periodontal pharmacotherapy - an updated review

Periodontal disease is mainly associated with the activity of bacteria which adhere to the tooth surface and form specific structure of bacterial biofilm. Periodontal bacteria cause inflammation of the gums and aggressive immune response, affecting the periodontium. The first phase of initial therapy - mechanical removal of dental plaque and calculus - is necessary. If this non-surgical therapy has proved to be unsuccessful, an alternative treatment with antimicrobial agents is then considered. Pharmacotherapy is based on systemic or local antibiotics and/or antiseptics, which are applied according to the severity of the disease. A number of recent periodontal studies present some of the pharmacological agents, that are directed against bacteria or a host immune response, are often chosen as an adjunct treatment option, but none of these antimicrobials were established as 'a gold standard' in the periodontal treatment. This review provides some present recommendation of pharmacological strategies, with particular emphasis on systemic and local antimicrobial therapy of periodontal disease.     

Polyanionic collagen membranes for guided tissue regeneration: Effect of progressive glutaraldehyde cross-linking on biocompatibility and degradation

The ultimate goal of periodontal therapy is to control periodontal tissue inflammation and to produce predictable regeneration of that part of the periodontium which has been lost as a result of periodontal disease. In guided tissue regeneration membranes function as mechanical barriers, excluding the epithelium and gingival corium from the root surface and allowing regeneration by periodontal ligament cells. This report aims to study the effect of glutaraldehyde (GA) cross-linking on mineralized polyanionic collagen (PAC) membranes by conducting a histological evaluation of the tissue response (biocompatibility) and by assessing the biodegradation of subcutaneous membrane implants in rats. We studied six different samples: a PAC, a PAC mineralized by alternate soaking processes for either 25 or 75 cycles (PAC 25 and PAC 75, respectively) and these films cross-linked by GA. Inflammatory infiltrate, cytokine dosage, fibrosis capsule thickness, metalloproteinase immunohistochemistry and membrane biodegradation after 1, 7, 15 and 30 days were measured. The inflammatory response was found to be more intense in membranes without cross-linking, while the fibrosis capsules became thicker in cross-linked membranes after 30 days. The membranes without cross-linking suffered intense biodegradation, while the membranes with cross-linking remained intact after 30 days. The cross-linking with GA reduced the inflammatory response and prevented degradation of the membranes over the entire course of the observation period. These membranes are thus an attractive option when the production of new bone depends on the prolonged presence of a mechanical barrier.     

Cytological characteristics of the human periodontal fibroblasts

This review examines current concepts of functional morphology and molecular biology of periodontal fibroblasts. These cells appear to be the major cellular elements of human periodontium that realize its functions. Recent evidence on fibroblast structure, regeneration, synthetic and secretory activity, adhesion to various matrix components, migration, response to hormones, cytokines, growth factors and microbial products as well as on their interaction with other cellular elements of periodontium, is reviewed. On the basis of the newest findings on cellular and molecular biology, the concept of the central role of fibroblasts in the local network of cytokine regulation that controls the integrated function of periodontal cells, is formulated.     

Cell surface proteoglycan expression by human periodontal cells

Cell surface proteoglycans are known to be involved in many functions including interactions with components of the extracellular microenvironment and serve to influence cell shape, adhesion, proliferation, and differentiation. They also can act as co-receptors, to help bind and modify the action of various growth factors and cytokines. Despite their strategic location and relevance to cell function, few studies have considered the nature of the cell surface proteoglycans associated with cells of the periodontium. Due to the structural complexity and multiplicity of cell types in the periodontium, we have selected three different cell lines (gingival connective tissue fibroblast, periodontal ligament fibroblast, and osteoblast) which each represent the unique functions within the periodontium to study the expression of cell surface proteoglycans. We hypothesized that a number of cell surface proteoglycans will be expressed by human periodontal cells and these may be related to the source and function of the cell. Western blotting and RT-PCR methods were used to study the expression of five cell surface proteoglycans (syndecan-1, -2, -4, glypican and betaglycan) in three cell lines of human periodontal cells in vitro. Our results demonstrated the expression of protein cores for syndecan-1 (43 kDa), syndecan-2 (48 kDa), syndecan-4 (35 kDa), glypican (64 kDa), and betaglycan (100-110 kDa). RT-PCR results confirmed that all of these cells produced mRNA for the cell surface proteoglycans under study, of which syndecan-2 showed a significant difference in expression between the periodontal ligament fibroblasts, gingival fibroblasts and osteoblasts. We conclude that the presence of specific cell surface proteoglycans on periodontal cells implies a likely role for these molecules in cell-cell, cell-matrix interactions involved in periodontal disease and/or regeneration of the periodontium, of which they may have distinctive functions related to the source and function of these cells.     

Plasmin is essential in preventing periodontitis in mice

Periodontitis involves bacterial infection, inflammation of the periodontium, degradation of gum tissue, and alveolar bone resorption, which eventually leads to loss of teeth. To study the role of the broad-spectrum protease plasmin in periodontitis, we examined the oral health of plasminogen (Plg)-deficient mice. In wild-type mice, the periodontium was unaffected at all time points studied; in Plg-deficient mice, periodontitis progressed rapidly, within 20 weeks. Morphological study results of Plg-deficient mice revealed detachment of gingival tissue, resorption of the cementum layer, formation of necrotic tissue, and severe alveolar bone degradation. IHC staining showed massive infiltration of neutrophils in the periodontal tissues. Interestingly, doubly deficient mice, lacking both tissue- and urokinase-type plasminogen activators, developed periodontal disease similar to that in Plg-deficient mice; however, mice lacking only tissue- or urokinase-type plasminogen activator remained healthy. Supplementation by injection of Plg-deficient mice with human plasminogen for 10 days led to necrotic tissue absorption, inflammation subsidence, and full regeneration of gum tissues. Notably, there was also partial regrowth of degraded alveolar bone. Taken together, our results show that plasminogen is essential for the maintenance of a healthy periodontium and plays an important role in combating the spontaneous development of chronic periodontitis. Moreover, reversal to healthy status after supplementation of Plg-deficient mice with plasminogen suggests the possibility of using plasminogen for therapy of periodontal diseases.     

Cell Surface Proteoglycan Expression by Human Periodontal Cells

Cell surface proteoglycans are known to be involved in many functions including interactions with components of the extracellular microenvironment and serve to influence cell shape, adhesion, proliferation, and differentiation. They also can act as co-receptors, to help bind and modify the action of various growth factors and cytokines. Despite their strategic location and relevance to cell function, few studies have considered the nature of the cell surface proteoglycans associated with cells of the periodontium. Due to the structural complexity and multiplicity of cell types in the periodontium, we have selected three different cell lines (gingival connective tissue fibroblast, periodontal ligament fibroblast, and osteoblast) which each represent the unique functions within the periodontium to study the expression of cell surface proteoglycans. We hypothesized that a number of cell surface proteoglycans will be expressed by human periodontal cells and these may be related to the source and function of the cell. Western blotting and RT-PCR methods were used to study the expression of five cell surface proteoglycans (syndecan-1, -2, -4, glypican and betaglycan) in three cell lines of human periodontal cells in vitro. Our results demonstrated the expression of protein cores for syndecan-1 (43 kDa), syndecan-2 (48 kDa), syndecan-4 (35kDa), glypican (64 kDa), and betaglycan (100-110 kDa). RT-PCR results confirmed that all of these cells produced mRNA for the cell surface proteoglycans under study, of which syndecan-2 showed a significant difference in expression between the periodontal ligament fibroblasts, gingival fibroblasts and osteoblasts. We conclude that the presence of specific cell surface proteoglycans on periodontal cells implies a likely role for these molecules in cell-cell, cell-matrix interactions involved in periodontal disease and/or regeneration of the periodontium, of which they may have distinctive functions related to the source and function of these cells.