肥胖影响牙周组织再生的机制及治疗策略

肥胖是当今社会面临的重要健康问题, 可导致机体处于慢性低水平炎症状态, 是高血压、2型糖尿病、非酒精性脂肪性肝病等多种慢性疾病的诱因。牙周炎作为一种常见的口腔慢性感染性疾病, 临床上主要表现为牙龈炎症、牙周袋形成、牙槽骨吸收、牙齿松动等。牙周炎治疗的最终目的是实现缺损区域牙周组织的再生。肥胖作为牙周炎的一个重要危险因素, 可以通过多种方式影响牙周炎症微环境, 最终影响牙周组织再生的效果。因此, 本文将从肥胖与牙周组织再生的关系、肥胖影响牙周组织再生的机制、肥胖状态下牙周组织再生的治疗策略等方面进行综述, 以期为肥胖状态下牙周组织再生治疗提供新思路。     

牙周组织再生治疗中牙源性干细胞的研究进展

牙周炎是一种慢性炎症性疾病,它可以破坏牙周组织,甚至导致牙齿丧失。随着对其发病机理的深入研究．牙周治疗的重点已从阻止疾病发展转变为促进牙周组织的再生和重建。牙周组织工程技术已成为牙周组织再生治疗的发展方向。干细胞群体的选择是组织工程最关键的部分之一。牙源性干细胞因其优良的再生和分化潜能,成为牙周组织再生治疗的重要来源。本文就牙周组织再生治疗中牙源性干细胞的研究进展作一综述。     

炎症微环境影响牙周膜干细胞成骨分化的信号通路

牙周膜干细胞(PDLSC)应用于组织工程学是目前治疗牙周炎骨缺失最有前景的方法之一,然而目前体内应用PDLSC再生牙周组织的效果并不理想,这可能是PDLSC所处的炎症微环境影响其命运所致.因此,本文从信号通路方面,探讨炎症微环境对PDLSC成骨分化潜能的影响,为其应用于牙槽骨的再生修复提供理论依据.     

Hippo-YAP信号通路影响牙周组织炎症及再生的研究进展

牙周炎是一种常见的慢性炎症性疾病,可导致牙周支持组织进行性破坏,在控制炎症的基础上尽可能争取一定程度的牙周组织再生是牙周炎的治疗目标。Hippo信号通路是一条高度保守的信号通路,在机械传导、炎症、干细胞功能调控、细胞增殖和分化,以及肿瘤的发生、发展等过程中都起着重要的作用。本文综述了Hippo-YAP信号通路在牙周组织炎症及牙周组织再生中发挥的作用,以期为牙周炎的治疗提供新的思路。     

不同干细胞来源外泌体在牙周再生领域的研究进展

牙周炎是由牙菌斑中的微生物所引起的慢性感染性疾病,可引起牙周支持组织的炎症和破坏,是成年人失牙的最主要原因。良好的菌斑控制可有效抑制炎症进展,然而目前在临床诊疗中,尚难以获得稳定的、令人满意的牙周组织再生。外泌体是真核细胞分泌的一种细胞外膜性微囊泡,可作为干细胞旁分泌活动的一种重要形式参与多种组织的再生。外泌体的应用为牙周组织再生提供了一种新策略,本文对不同干细胞来源外泌体在牙周再生领域的研究进展进行综述。     

牙周组织再生——当前治疗策略和未来研究方向的思考

牙周炎所致的牙周组织慢性进行性破坏是成人牙齿缺失的主要原因。传统牙周治疗虽可控制牙周炎症、延缓或阻止疾病进程, 却不能使缺失的牙周组织获得良好的再生。以引导性牙周组织再生、牙周骨移植技术为代表的再生治疗策略, 虽可有效减小牙周骨下袋深度, 一定程度上恢复患牙牙周稳态, 却面临再生能力有限、可预见性差的困境, 特别是在恢复牙周组织的生理结构和功能上, 远未达到临床所期望的目标。利用组织工程的原理、技术和方法促进牙周组织再生的尝试, 在动物实验中已取得令人振奋的结果, 但临床转化中却面临巨大的困难和挑战。诱导机体自身干细胞归巢, 实现牙周组织内源性再生, 可避免细胞培养和移植等复杂程序, 有望加速牙周组织再生新技术、新方法临床转化的进程。由于口腔微环境和牙周局部条件的影响, 牙周组织再生的生物学基础差, 探索切实有效的再生策略, 挽救、守护天然牙, 在今后很长一段时间里, 都将是牙周病学基础和临床研究领域关注的难题, 任重而道远。     

牙龈卟啉单胞菌诱导的牙周微环境失调引发牙周炎的作用机制研究进展

牙周炎作为一种由多种微生物诱发的慢性炎症性疾病,其造成的牙周组织损伤常与宿主免疫反应所引发的炎症相关。研究发现,补体系统参与牙周炎的发生与发展,牙龈卟啉单胞菌（P.gingivalis）可以利用补体成分破坏宿主的免疫防御,造成牙周微环境失调,进而诱发牙周炎的发生。因此,探究P.gingivalis利用补体诱发牙周微环境失调的作用机制,可以为今后牙周治疗的防治提供新的途径。     

Th17细胞在牙周炎中的研究进展

牙周炎是以牙周组织炎症和牙槽骨破坏为主要特征的慢性炎症性破坏性疾病。近来研究发现Th17细胞存在于牙周炎的病变牙周组织中,提示Th17细胞参与牙周炎的发病过程。本文就Th17细胞在牙周炎发病中的作用进行综述。     

间充质干细胞在牙周组织再生中的临床转化研究及应用前景

牙周炎是发生于牙周支持组织的口腔感染性疾病, 其破坏牙齿周围软硬组织, 最终引发牙齿松动脱落。目前的临床治疗手段可有效控制牙周感染及炎症, 但对已遭到破坏的牙周组织, 由于受到牙周缺损局部状况和患者全身因素的影响, 传统牙周治疗方式尚不能达到满意且稳定的牙周组织再生。近年基于间充质干细胞(mesenchymal stem cells, MSC)的牙周组织再生治疗代表了一种很有前景的治疗策略, 在现代再生医学中发挥了不可忽略的作用。本文结合近10年MSC在牙周组织工程中的临床转化应用研究及本课题组前期研究成果, 对MSC促进牙周组织再生的机制、MSC在牙周组织再生治疗中的临床前研究、临床转化研究及MSC未来的应用前景进行总结和阐述, 以期为后续开展MSC相关研究及临床试验提供参考。     

微环境对牙周膜干细胞分化的抑制和诱导作用

牙周膜干细胞(PDLSC)在牙周组织缺损修复和维持牙周动态平衡中起关键性的作用,是牙周组织再生修复治疗的基础细胞.在不同微环境作用下,PDLSC的增殖分化特性呈现出较大的差别.牙周膜干细胞龛和炎症等微环境对PDLSC的分化有抑制作用,然而,牙本质微环境及发育期根尖微环境能促进PDLSC的分化.研究不同的微环境对PDLSC功能的影响,一方面有助于深入研究PDLSC的生物学功能,另一方面为PDLSC应用于牙周疾病的再生治疗提供理论依据.本文就不同的微环境对PDLSC分化的抑制和诱导作用研究进展作一综述,并展望PDLSC在牙周缺损再生治疗中的应用前景.     

Stem cells and periodontal regeneration

Periodontitis is an inflammatory disease which manifests clinically as loss of supporting periodontal tissues including periodontal ligament and alveolar bone. For decades periodontists have sought ways to repair the damage which occurs during periodontitis. This has included the use of a range of surgical procedures, the use of a variety of grafting materials and growth factors, and the use of barrier membranes. To date periodontal regeneration is considered to be biologically possible but clinically unpredictable. Recently, reports have begun to emerge demonstrating that populations of adult stem cells reside in the periodontal ligament of humans and other animals. This opens the way for new cell-based therapies for periodontal regeneration. For this to become a reality a thorough understanding of adult human stem cells is needed. This review provides an overview of adult human stem cells and their potential use in periodontal regeneration.     

非编码RNA调控人牙周膜干细胞成骨向分化的研究进展

牙周炎是一种常见的炎症性疾病,以牙齿支持结构的进行性损伤为特点,是我国成人牙齿丧失的主要原因。治疗牙周炎的目的不仅是通过控制炎症来阻止疾病发展,更重要的是获得牙周再生。人牙周膜干细胞具有成骨向分化潜能,有望在牙周组织修复再生的临床应用上发挥重要作用。非编码RNA(ncRNA)一般是指不编码蛋白质的RNA。伴随高通量检测技术的不断发展,发现了大量的种类丰富的ncRNA,其生物学功能也被不断揭示。越来越多证据显示,ncRNA在分子机制及细胞组织层面对疾病的发生、发展起重要调控作用,因此探索ncRNA调控机制可为牙周再生的研究提供新思路。本综述主要阐述了目前研究较多的几种ncRNA在人牙周膜干细胞成骨向分化中的调控机制。     

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。     

Periodontal ligament stem cells: an update and perspectives

Chronic periodontitis is a serious infectious and inflammatory oral disease of humans worldwide. Conventional treatment modalities are effective for controlling periodontal disease. However, the regeneration of damaged periodontal tissues remains a major challenge in clinical practice due to the complex structure of the periodontium. Stem cell‐based regenerative approaches combined with the usage of emerging biomaterials are entering a new era in periodontal regeneration. The present review updates the current knowledge of periodontal ligament stem cell‐based approaches for periodontal regeneration, and elaborates on the potentials for clinical application.     

Stem cell‐based tooth and periodontal regeneration

Currently regeneration of tooth and periodontal damage still remains great challenge. Stem cell‐based tissue engineering raised novel therapeutic strategies for tooth and periodontal repair. Stem cells for tooth and periodontal regeneration include dental pulp stem cells (DPSCs), periodontal ligament stem cells (PDLSCs), stem cells from the dental apical papilla (SCAPs), and stem cells from human exfoliated deciduous teeth (SHEDs), dental follicle stem cells (DFSCs), dental epithelial stem cells (DESCs), bone marrow mesenchymal stem cells (BMMSCs), adipose‐derived stem cells (ADSCs), embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs). To date, substantial advances have been made in stem cell‐based tooth and periodontal regeneration, including dentin–pulp, whole tooth, bioroot and periodontal regeneration. Translational investigations have been performed such as dental stem cell banking and clinical trials. In this review, we present strategies for stem cell‐based tissue engineering for tooth and periodontal repair, and the translational studies.     

Identification of multipotent stem cells from adult dog periodontal ligament

Periodontal diseases, which are characterized by destruction of the connective tissues responsible for restraining the teeth within the jaw, are the main cause of tooth loss. Periodontal regeneration mediated by human periodontal ligament stem cells (hPDLSCs) may offer an alternative strategy for the treatment of periodontal disease. Dogs are a widely used large-animal model for the study of periodontal-disease progression, tissue regeneration, and dental implants, but little attention has been paid to the identification of the cells involved in this species. This study aimed to characterize stem cells isolated from canine periodontal ligament (cPDLSCs). The cPDLSCs, like hPDLSCs, showed clonogenic capability and expressed the mesenchymal stem cell markers STRO-1, CD146, and CD105, but not CD34. After induction of osteogenesis, cPDLSCs showed calcium accumulation in vitro. Moreover, cPDLSCs also showed both adipogenic and chondrogenic potential. Compared with cell-free controls, more cementum/periodontal ligament-like structures were observed in CB-17/SCID mice into which cPDLSCs had been transplanted. These results suggest that cPDLSCs are clonogenic, highly proliferative, and have multidifferentiation potential, and that they could be used as a new cellular therapeutic approach to facilitate successful and more predictable regeneration of periodontal tissue using a canine model of periodontal disease.     

牙周组织工程研究新进展

牙周炎是累及4种牙周支持组织的炎症性、破坏性疾病,现在包括GTR手术等传统的牙周治疗手段通常不能实现已破坏的牙周组织完全再生。近年来,大量的促进牙周再生方面的研究集中在牙周组织工程方面。本文就牙周组织工程的研究现状做一综述。     

Epigenetic regulation of osteogenic differentiation of periodontal ligament stem cells in periodontitis

Periodontitis is an inflammatory disease characterized by alveolar bone loss. Periodontal ligament stem cells (PDLSCs) have osteogenic differentiation potential, which can be influenced by epigenetics regulation in periodontitis. Therefore, this review aimed to shed light on the role of different epigenetic mechanisms in the osteogenic differentiation of PDLSCs and to consider the prospects of their possible therapeutic applications in periodontitis. Databases MEDLINE (through PubMed) and Web of Science were searched for the current knowledge of epigenetics in osteogenic differentiation of PDLSCs using the keywords “periodontal ligament stem cells”, “epigenetic regulation”, “epigenetics”, “osteogenic differentiation”, and “osteogenesis”. All studies introducing epigenetic regulation and PDLSCs were retrieved. This review shows that epigenetic factors like DNMT, KDM6A, HDACi, some miRNAs, and lncRNAs can induce the osteogenic differentiation of PDLSCs in the noninflammatory microenvironment. However, the osteogenic differentiation of PDLSCs is inhibited in the inflammatory microenvironment through the upregulated DNA methylation of osteogenesis-related genes and specific changes in histone modification and noncoding RNA. Epigenetics of osteogenic differentiation of PDLSCs in inflammation exhibits the contrary effect compared with a noninflammatory environment. The application of epigenetic drugs to regulate the abnormal epigenetic status in periodontitis and focus on alveolar bone regeneration is promising.     

Putative stem cells in regenerating human periodontium

Background and Objective:  Human postnatal stem cells have been identified in periodontal ligament, with the potential to regenerate the periodontium in vivo . However, it is unclear if periodontal ligament stem cells are present in regenerating periodontal tissues. The aim of this study was to identify and localize putative stem cells in block biopsies and explant cultures of regenerating human periodontal tissues.
Material and Methods:  Guided tissue regeneration was carried out on the molars of three human volunteers. After 6 wk, the teeth with the surrounding regenerating tissues and bone were surgically removed and processed for immunohistochemistry. The mesenchymal stem cell-associated markers STRO-1, CD146 and CD44 were used to identify putative stem cells. Cell cultures established from regenerating tissue explants were analysed by flow cytometry to assess the expression of these markers. Mineralization, calcium concentration and adipogenic potential of regenerating tissue cells were assessed and compared with periodontal ligament stem cells, bone marrow stromal stem cells and gingival fibroblasts.
Results:  STRO-1⁺, CD44⁺ and CD146⁺ cells were identified in the regenerating tissues. They were found mainly in the paravascular and extravascular regions. Flow cytometry revealed that cultured regenerating tissue cells expressed all three mesenchymal stem cell associated markers. The regenerating tissue cells were able to form mineral deposits and lipid-containing adipocytes. However, the level of mineralization in these cells was lower than that of periodontal ligament stem cells and bone marrow stromal stem cells.
Conclusion:  Cells with characteristics of putative mesenchymal stem cells were found in regenerating periodontal tissues, implying their involvement in periodontal regeneration.