经典Wnt信号通路与牙周膜干细胞成骨分化

牙周炎是口腔最常见的疾病之一,累及牙周支持组织,随着疾病的进展将引起附着丧失、牙周袋形成、牙槽骨吸收,最终导致牙齿松动脱落。因被牙周炎破坏吸收的牙槽骨自愈能力十分有限,所以牙周炎的治疗目标是在彻底清除菌斑生物膜的基础上,争取获得较多的牙周组织再生。牙周膜干细胞作为最适宜进行牙周组织再生的细胞,被广泛研究。Wnt信号通路分为经典Wnt通路和非经典Wnt信号通路,为十分复杂而高度保守的通路传导途径。该通路与牙周膜干细胞成骨分化的关系十分密切,牙周膜干细胞的成骨分化又对牙周组织再生有重要意义。该文对经典Wnt信号通路与牙周膜干细胞成骨分化的研究概况作一综述。     

微小RNA调控牙周膜干细胞成骨分化的研究进展

牙周炎是一种常见的慢性感染性疾病,可导致牙周支持组织的进行性破坏.牙周膜干细胞具有成骨向分化能力,在牙周组织再生领域中拥有广阔的应用前景.微小RNA(microRNA,miRNA)是长度约18～25个核苷酸的非编码单链RNA,可靶向mRNA 3'非翻译区(untranslated region,UTR),进而导致mRN...     

牙周相关长链非编码RNA研究进展

长链非编码RNA是指一类长度大于200个核苷酸、不编码蛋白质的RNA。研究证实，长链非编码RNA通过信号分子、诱饵分子、引导分子、支架分子等方式对遗传、转录及转录后水平等多层面进行调控。近年来，长链非编码RNA在牙周炎发生发展中的作用成为研究热点之一，文章就与牙周相关的长链非编码RNA在牙周组织炎症和牙周膜干细胞成骨中作用的研究进展做一综述。     

靶向Wnt信号通路在牙周炎治疗领域的研究现状

牙周炎是由菌斑细菌引起并最终导致牙周支持组织吸收的感染性疾病,其药物治疗主要分为抑制炎症反应和介导牙周组织修复两个方面。 Wnt信号通路是调控胚胎干细胞以及多种组织干细胞自我更新和分化的关键途径,被认为是生物体中最为重要的信号通路之一。一些研究显示,Wnt信号通路在牙周炎的发生和治疗中起到关键作用。本综述从牙周病炎症免疫反应和介导牙周膜细胞成骨分化两个方面介绍了近年来关于Wnt信号通路调控的研究成果,并比较了可能通过激活Wnt通路介导牙周膜细胞成骨分化的潜在药物,为靶向Wnt通路治疗牙周炎提供了依据。     

BMAL1基因对骨髓间充质干细胞成骨分化的调控作用

牙周炎是以牙周组织破坏为特征的感染性疾病,作为重要的牙周组织再生种子细胞,骨髓间充质干细胞在重构牙周组织结构和功能、促进牙周病好转乃至愈合方面具有重要作用,因此骨髓间充质干细胞的特性尤其是其成骨分化的相关调控机制是目前研究热点之一。BMAL1基因与骨髓间充质干细胞成骨分化等诸多生理行为的调控关系密切,有望成为牙周疾病新的治疗靶点。本文对BMAL1基因的特性以及调控骨髓间充质干细胞成骨分化的机制作一综述。     

慢性牙周炎中肿瘤坏死因子ɑ对骨髓间充质干细胞成骨分化的调控作用

骨髓间充质干细胞（BMSCs）在重构牙周组织结构和功能、促进牙周炎好转乃至愈合方面发挥重要作用,因此BMSCs的特性尤其是其成骨分化的调控机制是目前的研究热点。肿瘤坏死因子α（TNF-α）是牙周组织炎症微环境中的主要促炎因子,与BMSCs的成骨分化密切相关。探究TNF-α调控BMSCs成骨分化的机制有助于明确牙周炎的发病机制,寻找牙周疾病新的治疗靶点,改善牙周炎的治疗效果。本文将针对TNF-α在牙周炎发生发展过程中发挥的重要作用尤其是调控BMSCs成骨分化的可能机制作一综述。     

口腔干细胞成骨分化过程中非编码RNA作用的研究进展

应用口腔种植技术能够有效修复牙列缺损和牙列缺失。与传统修复方法相比,种植体更加美观、固位力强、咀嚼效率高、异物感小,并且可延缓牙槽骨的吸收。参与种植修复过程的口腔特有的干细胞具有快速增殖、迁移、成骨分化及矿化能力,其中成骨分化能力是影响种植体骨结合稳定程度的一个关键因素,直接影响口腔修复进程。非编码RNA（non-coding RNA,ncRNA）是一类不具备编码功能的RNA,其可在转录及转录后水平调控多种细胞的成骨分化。目前报道较多的ncRNA主要有微小RNA（microRNA,miRNA）、长链非编码RNA（long non-coding RNA,lncRNA）和环状RNA（circular RNA,circRNA）。文章对成骨分化过程中ncRNA作用的研究进展进行综述。     

非编码RNA调控牙囊干细胞成骨分化的研究进展

牙槽骨缺损的再生治疗一直是口腔领域亟待攻克的难点.牙周组织工程技术的出现为解决牙槽骨缺损提供了新思路,其中良好的种子细胞是实现组织再生的关键要素.牙囊干细胞(DFSC)具有成骨分化潜能,且易于获取和保存,是极具开发前景的种子细胞.DFSC成骨分化过程涉及复杂的基因调控,其中非编码RNA(ncRNA)作为一类从DNA转录...     

长链非编码RNA在干细胞成骨分化中作用机制的研究进展

在骨相关疾病治疗和骨组织工程中,干细胞作为成骨细胞的主要来源发挥着重要作用.长链非编码RNA(long non?coding RNA,lncRNA)可调控细胞周期、增殖代谢及谱系分化.随着高通量测序等研究技术的发展,lncRNA被发现可广泛参与干细胞的成骨调节.miRNA海绵作用是lncRNA调控成骨最经典的机制,近年...     

miR-203介导TNFα调控牙周膜干细胞成骨分化

目的:体外研究miR-203介导TNFα调控人牙周膜干细胞(human periodontal ligament stem cell,hPDLSCs)成骨分化能力及其分子机制.方法:qPCR检测人牙周膜干细胞成骨诱导前后TNFα和成骨基因的表达;qPCR及茜素红染色检测TNFα对牙周膜干细胞成骨分化能力及miR-203...     

The signaling pathways involved in non-coding RNA regulation during osteogenic differentiation of periodontal tissue-derived cells in the field of periodontitis

Periodontitis is a prevalent oral disease caused by chronic inflammation of the periodontal tissues surrounding the teeth, which can lead to bone loss, tooth loosening, and even tooth loss. This inflammation has a negative impact on the osteogenic differentiation capacity of periodontal tissue-derived cells. Non-coding RNAs (ncRNAs) are a class of RNA molecules that do not encode proteins but can regulate various physiological processes. In this review, we summarized the critical signaling pathways that ncRNAs modulate in osteogenic differentiation of periodontal tissue-derived cells, such as the Wnt, BMP/Smad, NF-κB, and PI3-K/Akt/mTOR pathways. This comprehensive exploration of ncRNA-mediated modulation offers fresh and promising insights for prospective approaches in the management of periodontitis and the advancement of periodontal regeneration therapies.     

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.     

A Synthetic Oligopeptide Derived From Enamel Matrix Derivative Promotes the Differentiation of Human Periodontal Ligament Stem Cells Into Osteoblast‐Like Cells With Increased Mineralization

Background: In a previous study, the authors obtained a synthetic peptide (SP) for useful periodontal tissue regeneration. Periodontal ligament stem cells (PDLSCs) have multiple potentiality to contribute to tissue regeneration. The aim of this experiment is to investigate the effect of SP on human PDLSCs. Methods: Periodontal ligament cells were obtained from healthy adult human third molars and used to isolate single PDLSC‐derived colonies. The mesenchymal stem cell nature of the PDLSCs was confirmed by immunohistochemical evaluation of STRO‐1 expression. Proliferation and osteoblastic differentiation were investigated by culturing PDLSCs in normal or osteogenic medium with and without SP (100 ng/mL). Osteoblast differentiation was assessed by measuring alkaline phosphatase (ALP) activity, osteocalcin production, mRNA expression of osteonectin, mineralization, and calcium deposition. Results: Isolated PDLSCs were immunohistochemically positive for vimentin and STRO‐1 and negative for cytokeratin. A greater number of calcified nodules were observed in osteogenic medium culture with SP than without. In the early and later stages of PDLSC culture with SP, osteonectin production and osteocalcin production were increased. SP in culture with osteogenic medium significantly enhanced proliferation of PDLSCs, as well as ALP activity, expression of osteonectin, osteocalcin production, formation of calcified nodules, and mineralization. Conclusions: SP enhances the formation of calcified nodules and osteocalcin production in the culture of PDLSCs into osteoblast‐like cells and is a useful material for periodontal tissue regeneration.     

年龄因素对人牙周膜干细胞培养和性能的影响

目的:探讨年龄因素对人牙周膜干细胞(periodontal ligament stem cells,PDLSCs)体外培养及其生物学特性的影响。方法:收集临床<30岁、>50岁具有完整牙根的第三磨牙各4个,分别刮取根面残留牙周膜进行PDLSCs分离培养,观察其细胞克隆形成能力、MTT方法检测生长曲线、流式细胞仪分析细胞表面分子,并进行体外成骨、成脂诱导,对比分析PDLSCs多向分化能力。结果:两组第三磨牙中均可培养出具有明显间充质干细胞(mesenchymal stem cell,MSC)特性的PDLSCs,但>50岁组获得的PDLSCs克隆形成率显著降低(P<0.05),其增殖、分化能力亦较<30岁组明显减弱(P<0.05)。结论:年龄因素对PDLSCs体外培养及其生物学特性具有明显影响;PDLSCs的基础和临床研究中,应充分考虑到病人年龄因素。     

小肠黏膜下层对牙周膜干细胞体外增殖、骨向分化的影响

目的 观察小肠黏膜下层 (SIS)与人牙周膜干细胞(PDLSCs)的生物相容性及其作为支架材料对PDLSCs的骨向分化诱导作用。方法 体外分离培养 PDLSCs,分别用四唑盐比色法（MTS）、茜素红染色法、碱性磷酸酶(ALP)和逆转录聚合酶链式反应（RT-PCR）方法观察 SIS 生物材料对PDLSCs增殖活性和骨向分化能力的影响。结果 SIS 显著地刺激体外培养的PDLSCs增殖,诱导了细胞的矿化和提高细胞ALP活性。RT-PCR结果显示SIS诱导后细胞 mRNA 水平表达骨涎蛋白(BSP)和骨钙素（OCN)。结论 体外培养条件下,SIS与PDLSCs有良好的生物相容性,能够诱导PDLSCs骨向分化。     

High Glucose Concentrations Suppress the Proliferation of Human Periodontal Ligament Stem Cells and Their Differentiation Into Osteoblasts

Background: Diabetes mellitus (DM) is a major risk factor for periodontal disease and affects various cellular functions. Periodontal ligament stem cells (PDLSCs) play an important role in periodontal tissue regeneration; however, the effect of hyperglycemia on PDLSCs is unclear. The aim of this study is to investigate whether hyperglycemia affects periodontal tissue regeneration, using human PDLSCs and high‐glucose medium as a model of DM. Methods: PDLSCs were obtained from healthy adult human mandibular third molars. Cell proliferation, osteoblastic differentiation, and proinflammatory cytokine expression were investigated by culturing PDLSCs in media supplemented with four different glucose concentrations representative of control patients (5.5 mM), patients with postprandial or controlled DM (8.0 mM), and patients with uncontrolled DM (12.0 and 24.0 mM). The molecular effects of hyperglycemia on PDLSC physiology were examined with a focus on the nuclear factor (NF)‐(κB signaling pathway. The involvement of NF‐κB was investigated with a specific NF‐κB inhibitor in PDLSCs under hyperglycemic conditions. Results: High glucose levels inhibited PDLSC proliferation and differentiation into osteoblasts but induced NF‐κB activation and subsequent interleukin (IL)‐6 and IL‐8 expression. Treatment with an NF‐κB inhibitor rescued the defects in cell proliferation and osteoblastic differentiation and inhibited the IL‐6 expression caused by the high‐glucose environment. Conclusion: The results of this study demonstrate that hyperglycemia inhibits human PDLSC proliferation and osteoblastic differentiation.     

化脓链球菌脂磷壁酸对人牙周膜干细胞分化能力的影响

目的 研究脂磷壁酸(LTA)对牙周膜干细胞(PDLSCs) 分化能力的影响,从而探讨G+细菌毒素LTA对人牙周膜干细胞再生牙周组织的影响.方法 用0.1、1和10μg/ml的LTA作用于PDLSCs,采用MTT方法及流式细胞术检测细胞的增殖及凋亡情况,使用碱性磷酸酶染色和茜素红染色对细胞的成骨分化能力进行比较;应用油红O染色鉴定成脂分化能力,实时定量PCR检测成骨成脂相关基因的变化,研究LTA在PDLSCs分化中的作用.结果 1μg/ml及10μg/ml LTA显著降低PDLSCs增殖率,细胞凋亡增加.ALP染色及活性结果表明,早期成骨能力各组之间没有显著差异;茜素红染色结果及钙离子浓度定量测定显示,随LTA浓度升高,PDLSCs晚期成骨能力降低,并具有LTA浓度依赖性.成骨相关基因Runx2表达表现相同变化趋势.油红O染色结果表明,随着LTA浓度的增加,PDLSCs的成脂分化能力升高,成脂相关基因PPARγ表达升高,具有LTA浓度依赖性.结论 LTA降低PDLSCs成骨分化能力,同时促进细胞成脂分化能力,表明LTA抑制PDLSCs介导的牙周组织再生.