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Enhanced regenerative potential of human dental pulp stem cells for the pulp-dentin complex through coculture with iPSC-derived endothelial cells: An in vitro study 通过与ipsc来源的内皮细胞共培养增强人牙髓干细胞对牙髓-牙本质复合体的再生潜力:一项体外研究
IF 2.1 4区 医学 Q2 DENTISTRY, ORAL SURGERY & MEDICINE Pub Date : 2025-10-02 DOI: 10.1016/j.archoralbio.2025.106409
Hsu Myat Cho , Ukseong Kim , Sunil Kim , Stephanie Myeong Choi , Sukjoon Lee , Euiseong Kim

Objectives

Although cell-based therapies using human dental pulp stem cells (hDPSCs) with other cell lineages and growth factors show promise in regenerative endodontics, combining hDPSCs with induced pluripotent stem cell-derived endothelial cells (iPSC-ECs) is unexplored. Moreover, iPSC-ECs overcome ethical and practical challenges related to primary endothelial cells. This study explored the odontogenic and angiogenic potential of hDPSCs and iPSC-ECs in direct coculture.

Design

hDPSCs were isolated from extracted human teeth, and iPSC‑ECs were generated via episomal reprogramming of hDPSCs followed by endothelial differentiation. Four groups were established for differentiation assays: hDPSCs in basal medium, osteogenic medium, modified osteogenic medium (D‑MOD), and coculture with iPSC‑ECs (1:5) in D‑MOD. Mineralization was assessed by alkaline phosphatase and alizarin red S staining; gene expression of odontogenic (DSPP, IBSP, ALPL) and angiogenic (PECAM1, MCAM, KDR) markers was measured by RT‑qPCR; protein levels were evaluated by Western blot and nestin immunofluorescence; and angiogenic capacity in the D‑MOD and coculture groups was quantified via Matrigel tube‑formation assay.

Results

The coculture group showed enhanced mineralization and significantly increased expression of DSPP, IBSP, and PECAM1. Protein analysis confirmed elevated DSPP and nestin levels. Tube formation assays revealed significantly more junctions, segments, and meshes in the coculture group.

Conclusions

This study demonstrated in vitro that coculturing hDPSCs with iPSC-ECs enhances both odontogenic and angiogenic differentiation compared to hDPSCs cultured alone. These findings highlight the potential of iPSC technology in regenerative endodontics and indicate a promising cell-based approach for future therapeutic applications.
目的:尽管利用人牙髓干细胞(hDPSCs)与其他细胞系和生长因子的细胞为基础的治疗方法在再生牙髓学中显示出前景,但hDPSCs与诱导多能干细胞衍生内皮细胞(iPSC-ECs)的结合尚未探索。此外,iPSC-ECs克服了与原代内皮细胞相关的伦理和实践挑战。本研究探讨了hdpsc和iPSC-ECs直接共培养的成牙潜能和血管生成潜能。设计:从提取的人牙齿中分离出hdpsc,通过hdpsc的局部重编程和内皮分化生成iPSC - ECs。建立四组进行分化试验:hdpsc在基础培养基、成骨培养基、改良成骨培养基(D - MOD)中,与iPSC - ECs在D - MOD中共培养(1:5)。碱性磷酸酶和茜素红S染色评价矿化;RT - qPCR检测牙源性(DSPP、IBSP、ALPL)和血管生成性(PECAM1、MCAM、KDR)标志物的基因表达;Western blot和nestin免疫荧光法检测蛋白水平;D - MOD组和共培养组的血管生成能力通过Matrigel成管试验进行量化。结果:共培养组矿化度增强,DSPP、IBSP、PECAM1表达显著升高。蛋白分析证实DSPP和巢蛋白水平升高。试管形成试验显示,共培养组中有更多的连接、节段和网格。结论:本研究表明,与单独培养的hdpsc相比,hdpsc与iPSC-ECs共培养可增强成牙和血管分化。这些发现强调了iPSC技术在再生牙髓学中的潜力,并指出了一种有前途的基于细胞的治疗方法。
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引用次数: 0
Morphological traits and caries susceptibility of the cusp of carabelli in permanent maxillary molars: A study in Lahore, Pakistan 巴基斯坦拉合尔地区恒上颌磨牙牙尖形态特征及龋易感性的研究
IF 2.1 4区 医学 Q2 DENTISTRY, ORAL SURGERY & MEDICINE Pub Date : 2025-09-27 DOI: 10.1016/j.archoralbio.2025.106406
Maliha Shahbaz , Naauman Zaheer , Usman Zaheer , Madiha , Muhammad Haris Bilal , Abdullah Sajid , Junaid Ali , Hareem Aziz , Khurram Nadeem

Objective

To evaluate the prevalence, morphological traits, and caries susceptibility of the Cusp of Carabelli (CoC) in permanent maxillary molars among patients in Lahore, Pakistan.

Design

A descriptive cross-sectional study was conducted among 432 participants aged 12 years or older at Lahore Medical and Dental College. Clinical examination of maxillary first and second molars was performed using the Arizona State University Dental Anthropology System (ASUDAS) for CoC traits and the International Caries Detection and Assessment System (ICDAS) for caries assessment. Inter- and intra-examiner calibration ensured diagnostic reliability (Cohen's Kappa >0.90).

Results

CoC (ASUDAS grades 1–7) was observed in 201 individuals (46.5 %) on maxillary first molars and in 7 individuals (1.6 %) on second molars, with bilateral expression more common than unilateral. The right first molar showed a higher prevalence of CoC and caries incidence. Morphological traits ranged from subtle grooves to pronounced cusps, with small vertical grooves (ASUDAS 1) being the most frequent. Caries susceptibility correlated positively with CoC prominence (p < 0.001). Multivariate logistic regression identified CoC grade as the strongest predictor of caries, overshadowing age, side, and molar position, and substantially improving model sensitivity (0 % to 97.2 %).

Conclusion

CoC is a prevalent trait and is significantly associated with early-stage dental caries in maxillary first molars. Its presence, particularly in prominent forms, may pose an increased risk of caries. These findings underscore the need for enhanced preventive strategies and clinical attention in individuals with CoC.
目的了解巴基斯坦拉合尔地区上颌恒磨牙Carabelli尖(CoC)的患病率、形态特征及龋易感性。设计在拉合尔医学和牙科学院对432名12岁或以上的参与者进行了一项描述性横断面研究。采用亚利桑那州立大学口腔人类学系统(ASUDAS)对上颌第一、第二磨牙进行CoC特征的临床检查,采用国际龋齿检测与评估系统(ICDAS)对龋齿进行评估。审查员之间和内部的校准确保了诊断的可靠性(Cohen's Kappa >0.90)。结果上颌第一磨牙有201例(46.5 %)、第二磨牙有7例(1.6 %)出现scoc (ASUDAS分级1 ~ 7级),双侧表达较单侧多见。右第一磨牙CoC患病率和龋发病率较高。形态特征从细微的凹槽到明显的尖头,以小的垂直凹槽(ASUDAS 1)最为常见。龋易感性与CoC显著性呈正相关(p <; 0.001)。多变量logistic回归发现CoC分级是龋病、遮蔽年龄、侧边和磨牙位置的最强预测因子,并显著提高了模型敏感性(0 %至97.2% %)。结论coc是上颌第一磨牙早期龋病的普遍特征,与早期龋病有显著关系。它的存在,特别是突出的形式,可能会增加患龋的风险。这些发现强调需要加强对CoC患者的预防策略和临床关注。
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引用次数: 0
Endoplasmic reticulum stress as a nexus of temporomandibular joint osteoarthritis 内质网应激与颞下颌关节骨性关节炎的关系。
IF 2.1 4区 医学 Q2 DENTISTRY, ORAL SURGERY & MEDICINE Pub Date : 2025-09-26 DOI: 10.1016/j.archoralbio.2025.106407
Xinqi Huang , Zinan Cen , Xinxuan Zhou , Zhihe Zhao , Xiao Cen

Objective

This review aims to summarize the molecular architecture of endoplasmic reticulum (ER) stress signaling networks and their mechanistic involvement in temporomandibular joint osteoarthritis (TMJOA) progression, and current therapeutic strategies targeting ER stress mediators and the obstacles from bench to bedside.

Design

The related literatures of the roles of ER in TMJOA were searched through PubMed database by different combinations of the following keywords including animal models, ER, unfolded protein response (UPR), ER-associated degradation (ERAD), ER-phagy, TMJ, and OA. No filters were used in the search. The references of eligible studies were also analyzed and reviewed comprehensively.

Results

This review discussed how ER stress signaling orchestrated TMJOA pathogenesis, including UPR, ERAD, and ER-phagy. It was also summarized how biomechanical stress and hypoxic microenvironment synergistically exacerbated ER stress, and the current therapeutic strategies for TMJOA based on ER stress modulators and the obstacles in bench-to-bedside research.

Conclusions

ER proteostasis represented a pivotal but underexplored therapeutic axis in TMJOA. Bridging the gap between mechanistic understanding of ER stress adaptation and TMJ-specific pathobiology is essential for developing novel therapeutic strategies for TMJOA.
目的:综述内质网(ER)应激信号网络的分子结构及其在颞下颌关节骨性关节炎(TMJOA)进展中的机制,以及目前针对内质网应激介质的治疗策略和从实验台到床边的障碍。设计:通过动物模型、ER、未折叠蛋白反应(UPR)、ER相关降解(ERAD)、ER吞噬、TMJ、OA等关键词的不同组合,在PubMed数据库中检索ER在TMJOA中作用的相关文献。搜索中没有使用过滤器。并对符合条件的文献进行了综合分析和综述。结果:本文讨论了内质网应激信号如何调控TMJOA的发病机制,包括UPR、ERAD和ER吞噬。总结了生物力学应激和缺氧微环境如何协同加剧内质网应激,以及目前基于内质网应激调节剂的TMJOA治疗策略和从实验台到临床研究的障碍。结论:内质网蛋白酶抑制是TMJOA的关键治疗轴,但尚未得到充分研究。弥合内质网应激适应机制与tmj特异性病理生物学之间的差距对于开发新的TMJOA治疗策略至关重要。
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引用次数: 0
Antibacterial effects of charcoal and fluoride dentifrices in oral biofilms 活性炭和含氟牙膏在口腔生物膜中的抗菌作用。
IF 2.1 4区 医学 Q2 DENTISTRY, ORAL SURGERY & MEDICINE Pub Date : 2025-09-25 DOI: 10.1016/j.archoralbio.2025.106405
Ashley N. Bowers , Caroline Coradi Tonon , Sam Yeo , Kinga Vojnits , Rayhan Shah , Sepideh Pakpour , Simone Duarte

Objectives

Charcoal-containing dentifrices are increasingly popular for their whitening claims, but data on antimicrobial effects are limited. This study compared the antibacterial efficacy of charcoal dentifrices versus non-charcoal dentifrices containing sodium fluoride (NaF), stannous fluoride (SnF₂), or sodium monofluorophosphate (NaMFP) against multi-species oral biofilms.

Methods

Biofilms of Streptococcus mutans, S. gordonii, and S. sanguinis were grown on hydroxyapatite discs and treated for 60 s with 6 dentifrice slurries (3 charcoal, 3 non-charcoal dentifrices) or controls (saline and 0.12 % chlorhexidine, CHX). Antibacterial effects were assessed by CFU/mL; (n = 9/group) and qPCR (n = 3/group). For fluoride-type analyses, charcoal and non-charcoal dentifrices were combined (CFU n = 18/type; qPCR n = 6/type). Percent reduction was compared across groups using one-way ANOVA with post-hoc tests.

Results

NaF dentifrices exhibited the greatest overall antibacterial activity (46.8 % reduction), followed by NaMFP (34.9 %), while SnF₂ showed minimal effect (≤ 5.7 %). Charcoal inclusion did not enhance efficacy and slightly reduced NaF activity. Species-specific responses varied: NaF eliminated S. gordonii, and significantly reduced S. mutans and S. sanguinis. Charcoal inclusion did not significantly alter species-level viability. qPCR supported CFU trends but showed limited between-group differences. Overall, fluoride type – not charcoal – primarily determined efficacy (NaF > NaMFP > SnF2).

Conclusions

Fluoride type had a greater impact on antibacterial efficacy than charcoal. NaF was most effective, while SnF₂ least. Charcoal offered no benefit and may slightly diminish NaF performance. Fluoride choice is more critical than charcoal additives for caries prevention.
目的:含碳牙膏因其美白功效而越来越受欢迎,但有关抗菌效果的数据有限。本研究比较了木炭牙膏与含氟化钠(NaF)、氟化亚锡(SnF 2)或单氟磷酸钠(NaMFP)的非木炭牙膏对多种口腔生物膜的抗菌效果。方法:在羟基磷灰石盘上培养变形链球菌、哥氏链球菌和血链球菌的生物膜,用6种牙液(3种木炭牙液,3种非木炭牙液)或对照组(生理盐水和0.12 %氯己定,CHX)处理60 s。以CFU/mL评价抗菌效果;(n = 9/组)和qPCR (n = 3/组)。对于氟化物型分析,将木炭和非木炭牙膏组合使用(CFU n = 18/型;qPCR n = 6/型)。使用事后检验的单因素方差分析比较各组间减少的百分比。结果:NaF牙膏的整体抑菌活性最高(降低46.8% %),NaMFP次之(降低34.9% %),SnF 2的总体抑菌活性最低(≤5.7 %)。炭包合不提高疗效,并略微降低NaF活性。物种特异性反应各不相同:NaF消除了gordonii,并显著减少了S. mutans和S. sanguinis。炭包埋没有显著改变物种水平的生存能力。qPCR支持CFU趋势,但组间差异有限。总的来说,氟化物类型——而不是木炭——主要决定功效(NaF > NaMFP > SnF2)。结论:氟化物类型对抗菌效果的影响大于木炭。NaF效果最好,SnF效果最差。木炭没有任何好处,可能会略微降低NaF的性能。氟化物的选择比木炭添加剂在预防龋齿方面更为关键。
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引用次数: 0
OIP5-AS1 expression profiles in different stages of oral squamous cell carcinoma OIP5-AS1在口腔鳞状细胞癌不同分期中的表达谱
IF 2.1 4区 医学 Q2 DENTISTRY, ORAL SURGERY & MEDICINE Pub Date : 2025-09-24 DOI: 10.1016/j.archoralbio.2025.106403
Ameya K.P., Ashikha Shirin Usman P.P., Durairaj Sekar

Objectives

To investigate the expression patterns of long non-coding RNA OIP5-AS1 across various stages of oral squamous cell carcinoma (OSCC) and assess its potential as a biomarker and therapeutic target.

Design

A comprehensive review of recent literature focusing on OIP5-AS1's role in OSCC was conducted. Analysis included OIP5-AS1 expression levels in cancerous versus non-cancerous tissues and exploration of its interactions with tumor-suppressing microRNAs (miRNAs).

Results

OIP5-AS1 was found to be significantly upregulated in advanced stages of OSCC compared to non-cancerous tissues. Its function as a molecular sponge for miRNAs contributes to the promotion of tumorigenic pathways, complicating therapeutic responses and highlighting its role as an oncogene.

Conclusions

OIP5-AS1 is a critical player in the progression of OSCC, influencing tumor dynamics and mechanisms of resistance. Elucidating its expression patterns and functional roles suggests that OIP5-AS1 could serve as a valuable biomarker for early diagnosis and personalized treatment strategies.
目的研究长链非编码RNA OIP5-AS1在口腔鳞状细胞癌(OSCC)不同分期中的表达模式,并评估其作为生物标志物和治疗靶点的潜力。我们对近期关于OIP5-AS1在OSCC中的作用的文献进行了全面的回顾。分析包括OIP5-AS1在癌变组织和非癌变组织中的表达水平,并探索其与肿瘤抑制microRNAs (miRNAs)的相互作用。结果与非癌组织相比,soip5 - as1在晚期OSCC中表达明显上调。其作为mirna分子海绵的功能有助于促进致瘤途径,使治疗反应复杂化,并突出其作为癌基因的作用。结论soip5 - as1在OSCC的发展过程中起关键作用,影响肿瘤动力学和耐药机制。阐明其表达模式和功能作用表明OIP5-AS1可以作为早期诊断和个性化治疗策略的有价值的生物标志物。
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引用次数: 0
Expression patterns of desmosome family members during tooth development and the role of Desmocollin-3 in cytodifferentiation of stratum intermedium 牙齿发育过程中桥粒家族成员的表达模式及桥粒蛋白-3在中间层细胞分化中的作用。
IF 2.1 4区 医学 Q2 DENTISTRY, ORAL SURGERY & MEDICINE Pub Date : 2025-09-24 DOI: 10.1016/j.archoralbio.2025.106404
Triana Marchelina , Yuta Chiba , Shinji Otake , Li Wanshu , Hiroshi Sato , Yumiko Nakashima , Asuna Sugimoto , Tsutomu Iwamoto , Aya Yamada , Kan Saito , Satoshi Fukumoto

Objective

Desmocollin-3 (Dsc3), a desmosomal cadherin, is critical in maintaining epithelial cohesion and integrity. Despite its recognized function in skin and mucosal epithelium, its contribution to tooth development remains poorly understood. The study aims to identify stratum intermedium (SI)-specific markers using single-cell RNA-sequence (scRNA-seq) and to investigate the functional role of Dsc3 in maintaining SI cell integrity and differentiation.

Design

In this study, we pursued the marker genes of SI cells using scRNA-seq analysis of post-natal day 12 molar. Furthermore, we examined the role of the SI marker gene using dental epithelial cell line SF2.

Results

We found that desmosome family genes are highly expressed in SI cluster and among them, Dsc3 showed specific expression in SI cluster. Knockdown of Dsc3 in the SF2 epithelial cell line led to significantly smaller cell size, indicating impaired epithelial differentiation. The expression of SI marker genes was suppressed by the knockdown of Dsc3 with a marked loss of tight junction protein Tjp1 (ZO-1), indicating disrupted intercellular junctions and impaired epithelial barrier function. This disruption correlated with altered expression of key ameloblast differentiation markers, suggesting a failure in proper ameloblast lineage commitment, highlighting a disruption in the SI’s ability to support ameloblast lineage specification.

Conclusion

These findings indicate that Dsc3 is essential for SI structural integrity and its signaling support to ameloblasts.
目的:桥粒蛋白-3 (desmocolin -3, Dsc3)是一种桥粒体钙粘蛋白,对维持上皮内聚和完整性至关重要。尽管它在皮肤和粘膜上皮中具有公认的功能,但它对牙齿发育的贡献仍然知之甚少。本研究旨在利用单细胞rna序列(scRNA-seq)鉴定地层间质(SI)特异性标记,并研究Dsc3在维持SI细胞完整性和分化中的功能作用。设计:在本研究中,我们使用scRNA-seq分析出生后12天臼齿的SI细胞的标记基因。此外,我们用牙上皮细胞系SF2检测了SI标记基因的作用。结果:我们发现桥粒家族基因在SI簇中高表达,其中Dsc3在SI簇中特异性表达。在SF2上皮细胞系中敲低Dsc3导致细胞大小明显变小,表明上皮分化受损。SI标记基因的表达被Dsc3的敲低所抑制,紧密连接蛋白Tjp1 (ZO-1)的显著缺失,表明细胞间连接被破坏,上皮屏障功能受损。这种破坏与关键成釉细胞分化标志物的表达改变有关,表明成釉细胞谱系的正常承诺失败,突出了SI支持成釉细胞谱系规范的能力的破坏。结论:这些发现表明Dsc3对SI结构完整性及其对成釉细胞的信号支持至关重要。
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引用次数: 0
In Vitro antibacterial activity of Lactiplantibacillus sp. cell-free supernatants against Porphyromonas gingivalis: A potential approach for oral health 无细胞乳酸杆菌上清液对牙龈卟啉单胞菌的体外抗菌活性:一种潜在的口腔健康方法
IF 2.1 4区 医学 Q2 DENTISTRY, ORAL SURGERY & MEDICINE Pub Date : 2025-09-23 DOI: 10.1016/j.archoralbio.2025.106399
Hui Ying Yit , Zaleha Shafiei , Noraziah Mohamad Zin , Mazlina Mohd Said

Objective

This study explores the potential of postbiotic metabolites from lactic acid bacteria (LAB) isolated from human milk and tempeh against Porphyromonas gingivalis, a key pathogen in periodontitis.

Design

Selected LAB strains and their treated cell-free supernatants (TCFS), lyophilized TCFS (L-TCFS), and bacteriocin-like inhibitory substances (BLIS) were tested individually and in combination using agar well diffusion, MIC, MBC, autoaggregation, coaggregation, and biofilm inhibition assays. LAB identification was performed using the API 50 CHL kit and 16S rDNA sequencing.

Results

Strain S2, a mixture of Lactiplantibacillus sp. SUK1 and T2 showed the highest inhibitory activity (20.06 ± 4.14 mm) using the agar well diffusion method. It demonstrated strong autoaggregation compared to the individual T2 strain but lacked significant coaggregation ability. The L-TCFS of S2 also exhibited the strongest antibacterial effect, with a minimum inhibitory concentration (MIC) of 50 mg/mL, although no minimum bactericidal concentration (MBC) was detected for any bacteriocin-like inhibitory substances (BLIS). L-TCFS from strain S2 significantly reduced P. gingivalis biofilm formation at a minimum concentration of 25 mg/mL, compared to the untreated control. Strain T2 was identified as Lactiplantibacillus plantarum using the API 50CHL test and 16S rDNA gene sequencing.

Conclusion

The combination metabolite S2 demonstrates promising inhibitory activity against P. gingivalis and may serve as an effective adjunctive therapy for periodontal infections, outperforming individual and other combination LAB strains tested.
目的探讨乳酸菌(LAB)对牙周炎病原菌牙龈卟啉单胞菌(Porphyromonas龈卟啉单胞菌)的拮抗作用。设计选定的实验室菌株及其处理过的无细胞上清液(TCFS)、冻干TCFS (L-TCFS)和细菌素样抑制物质(BLIS)分别和联合使用琼脂孔扩散、MIC、MBC、自聚集、共聚集和生物膜抑制试验进行检测。使用API 50 CHL试剂盒和16S rDNA测序进行LAB鉴定。结果由乳酸菌SUK1和T2混合而成的S2菌株在琼脂孔扩散法下的抑菌活性最高(20.06±4.14 mm)。与单个T2菌株相比,它表现出较强的自聚集能力,但缺乏显著的共聚集能力。S2的L-TCFS也表现出最强的抑菌效果,最低抑菌浓度(MIC)为50 mg/mL,但未检测到任何细菌素样抑制物质(BLIS)的最低杀菌浓度(MBC)。与未处理的对照相比,菌株S2的L-TCFS在最低浓度为25 mg/mL时显著减少了牙龈卟啉卟啉菌生物膜的形成。菌株T2经API 50CHL检测和16S rDNA基因测序鉴定为植物乳杆菌。结论联合代谢产物S2对牙龈假单胞菌具有良好的抑制作用,可作为治疗牙周感染的有效辅助药物,其效果优于单个和其他联合LAB菌株。
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引用次数: 0
Molecular and thermal signatures of dental tissues in third molars: An in vitro comparative study using fourier-transform infrared spectroscopy and differential scanning calorimetry 第三磨牙牙组织的分子和热特征:傅里叶变换红外光谱和差示扫描量热法的体外比较研究。
IF 2.1 4区 医学 Q2 DENTISTRY, ORAL SURGERY & MEDICINE Pub Date : 2025-09-19 DOI: 10.1016/j.archoralbio.2025.106402
Rola Zahedah , Recep Üstünsoy , Aliye Tuğçe Gürcan , Bircan Dinç

Objective

To characterize and compare the molecular and thermal characteristics of enamel, dentin, cementum, and the dentin–pulp complex in permanent third molars using Fourier-transform infrared (FTIR) spectroscopy and differential scanning calorimetry (DSC).

Design

Samples from extracted third molars (n = 15) were prepared and analyzed using FTIR to assess molecular composition and DSC to evaluate thermal transitions, including dehydration, collagen degradation, and mineral phase transformation. All measurements were conducted in triplicate.

Results

FTIR revealed enamel as highly mineralized with minimal organic content, dentin and cementum as collagen-rich, and the dentin–pulp complex as a hybrid tissue. DSC analysis identified consistent thermal transitions: water loss (110–125 °C), collagen breakdown (300–320 °C), and mineral decomposition (455–470 °C). Enamel displayed the highest crystallinity, while cementum exhibited the highest enthalpy change. Tissues with stronger FTIR collagen peaks corresponded to higher DSC energy release during protein degradation.

Conclusion

Molecular and thermal profiling of dental tissues provide baseline reference data for biomaterial design and regenerative strategies.

Clinical significance

Understanding tissue-specific molecular and thermal properties can guide the development of biomimetic restorative materials, inform safer thermal thresholds during clinical procedures, and support diagnostic approaches for aging and pathological changes.
目的:采用傅里叶变换红外光谱(FTIR)和差示扫描量热法(DSC)对恒磨牙釉质、牙本质、牙骨质和牙本质-牙髓复合体的分子和热特性进行表征和比较。设计:制备提取的第三磨牙样品(n = 15),并使用FTIR评估分子组成,DSC评估热转变,包括脱水、胶原降解和矿物相变。所有测量一式三份。结果:FTIR显示牙釉质高度矿化,有机物含量极低,牙本质和牙骨质富含胶原蛋白,牙本质-牙髓复合体为杂交组织。DSC分析确定了一致的热转变:水分损失(110-125 °C),胶原蛋白分解(300-320 °C)和矿物质分解(455-470 °C)。釉质的结晶度最高,牙骨质的焓变最高。FTIR胶原蛋白峰较强的组织在蛋白质降解过程中相应的DSC能量释放较高。结论:牙组织的分子和热谱分析为生物材料设计和再生策略提供了基线参考数据。临床意义:了解组织特异性分子和热特性可以指导仿生修复材料的开发,在临床过程中提供更安全的热阈值,并支持衰老和病理变化的诊断方法。
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引用次数: 0
ZBP1-NLRP3 axis integrates PANoptosis and ferroptosis during inflammatory injury in human dental pulp fibroblasts ZBP1-NLRP3轴整合了人牙髓成纤维细胞炎症损伤过程中的PANoptosis和ferroptosis。
IF 2.1 4区 医学 Q2 DENTISTRY, ORAL SURGERY & MEDICINE Pub Date : 2025-09-19 DOI: 10.1016/j.archoralbio.2025.106398
Ai-E. He , Xing Wang , Ni Xie, Yun-He Xiao

Objective

To define how Z-DNA binding protein 1 (ZBP1) and NOD-like receptor family pyrin domain-containing 3 (NLRP3) signaling regulate lipopolysaccharide (LPS)-induced inflammation, PANoptosis, and ferroptosis in human dental pulp fibroblasts (HDPFs).

Design

HDPFs were treated with LPS, and ZBP1 and NLRP3 were silenced using small interfering RNA (siRNA), individually or in combination. Inflammatory mediators and death-pathway markers were quantified by quantitative real-time PCR (qRT-PCR), Western blotting, enzyme-linked immunosorbent assay (ELISA), and biochemical assays; Annexin V/propidium iodide flow cytometry assessed cell-death distributions.

Results:

LPS significantly increased ZBP1 and NLRP3 expression and elevated cytokine/chemokine release; each was attenuated by ZBP1 or NLRP3 knockdown, with the greatest reduction after dual silencing. LPS triggered PANoptosis, as indicated by increased Annexin V⁺/PI⁺ cell populations and upregulation of caspase-1, cleaved caspase-8, RIPK3, GSDMD, and p-MLKL/MLKL, which were significantly reduced by inhibition of the ZBP1-NLRP3 axis. Ferroptosis features were also evident after LPS, including impaired iron homeostasis (downregulated ferritin heavy chain 1 [FTH1] and ferroportin [FPN1] with Fe²⁺ accumulation), enhanced lipid peroxidation (upregulated ALOX15, LPCAT3, PTGS2 with increased malondialdehyde and lipid reactive oxygen species), and weakened antioxidant defenses (reduced glutathione peroxidase-4 [GPX4], solute carrier family 7 member 11 [SLC7A11], glutathione, and GPX4 activity). These changes were mitigated by single-gene silencing and most effectively by dual knockdown.

Conclusion

The ZBP1-NLRP3 axis acts upstream to coordinate LPS-induced PANoptosis and ferroptosis in HDPFs. Targeting this axis dampens inflammatory cell death and oxidative-metabolic dysregulation, highlighting a potential therapeutic strategy for pulpitis-related tissue injury.
目的:探讨Z-DNA结合蛋白1 (ZBP1)和nod样受体家族pyrin结构域3 (NLRP3)信号通路如何调控脂多糖(LPS)诱导的人牙髓成纤维细胞(HDPFs)炎症、PANoptosis和ferroptosis。设计:用LPS处理hdpf,用小干扰RNA (siRNA)单独或联合沉默ZBP1和NLRP3。采用实时荧光定量PCR (qRT-PCR)、免疫印迹法(Western blotting)、酶联免疫吸附法(ELISA)和生化法对炎症介质和死亡途径标志物进行定量分析;膜联蛋白V/碘化丙啶流式细胞术评估细胞死亡分布。结果:LPS显著增加ZBP1和NLRP3的表达,增加细胞因子/趋化因子的释放;通过敲除ZBP1或NLRP3,它们都被减弱,双重沉默后的减弱幅度最大。LPS触发PANoptosis, Annexin V + /PI +细胞数量增加,caspase-1、cleaved caspase-8、RIPK3、GSDMD和p-MLKL/MLKL表达上调,这些表达通过抑制ZBP1-NLRP3轴而显著降低。脂多糖后的铁中毒特征也很明显,包括铁体内平衡受损(铁蛋白重链1 [FTH1]和铁转运蛋白[FPN1]以Fe 2 +积累下调),脂质过氧化作用增强(ALOX15、LPCAT3、PTGS2上调,丙二醛和脂质活性氧增加),抗氧化防御能力减弱(谷胱甘肽过氧化物酶-4 [GPX4]、溶质载体家族7成员11 [SLC7A11]、谷胱甘肽和GPX4活性降低)。这些变化可以通过单基因沉默和双基因敲除来缓解。结论:ZBP1-NLRP3轴在lps诱导的HDPFs PANoptosis和ferroptosis中起上游协调作用。靶向该轴抑制炎症细胞死亡和氧化代谢失调,强调了牙髓炎相关组织损伤的潜在治疗策略。
{"title":"ZBP1-NLRP3 axis integrates PANoptosis and ferroptosis during inflammatory injury in human dental pulp fibroblasts","authors":"Ai-E. He ,&nbsp;Xing Wang ,&nbsp;Ni Xie,&nbsp;Yun-He Xiao","doi":"10.1016/j.archoralbio.2025.106398","DOIUrl":"10.1016/j.archoralbio.2025.106398","url":null,"abstract":"<div><h3>Objective</h3><div>To define how Z-DNA binding protein 1 (ZBP1) and NOD-like receptor family pyrin domain-containing 3 (NLRP3) signaling regulate lipopolysaccharide (LPS)-induced inflammation, PANoptosis, and ferroptosis in human dental pulp fibroblasts (HDPFs).</div></div><div><h3>Design</h3><div>HDPFs were treated with LPS, and <em>ZBP1</em> and <em>NLRP3</em> were silenced using small interfering RNA (siRNA), individually or in combination. Inflammatory mediators and death-pathway markers were quantified by quantitative real-time PCR (qRT-PCR), Western blotting, enzyme-linked immunosorbent assay (ELISA), and biochemical assays; Annexin V/propidium iodide flow cytometry assessed cell-death distributions.</div></div><div><h3>Results:</h3><div>LPS significantly increased ZBP1 and NLRP3 expression and elevated cytokine/chemokine release; each was attenuated by <em>ZBP1</em> or <em>NLRP3</em> knockdown, with the greatest reduction after dual silencing. LPS triggered PANoptosis, as indicated by increased Annexin V⁺/PI⁺ cell populations and upregulation of caspase-1, cleaved caspase-8, RIPK3, GSDMD, and p-MLKL/MLKL, which were significantly reduced by inhibition of the ZBP1-NLRP3 axis. Ferroptosis features were also evident after LPS, including impaired iron homeostasis (downregulated ferritin heavy chain 1 [FTH1] and ferroportin [FPN1] with Fe²⁺ accumulation), enhanced lipid peroxidation (upregulated ALOX15, LPCAT3, PTGS2 with increased malondialdehyde and lipid reactive oxygen species), and weakened antioxidant defenses (reduced glutathione peroxidase-4 [GPX4], solute carrier family 7 member 11 [SLC7A11], glutathione, and GPX4 activity). These changes were mitigated by single-gene silencing and most effectively by dual knockdown.</div></div><div><h3>Conclusion</h3><div>The ZBP1-NLRP3 axis acts upstream to coordinate LPS-induced PANoptosis and ferroptosis in HDPFs. Targeting this axis dampens inflammatory cell death and oxidative-metabolic dysregulation, highlighting a potential therapeutic strategy for pulpitis-related tissue injury.</div></div>","PeriodicalId":8288,"journal":{"name":"Archives of oral biology","volume":"180 ","pages":"Article 106398"},"PeriodicalIF":2.1,"publicationDate":"2025-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145152374","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Editorial on the special issue on temporomandibular disorders (TMD), AOB journal 关于颞下颌疾病(TMD)特刊的社论,AOB杂志
IF 2.1 4区 医学 Q2 DENTISTRY, ORAL SURGERY & MEDICINE Pub Date : 2025-09-19 DOI: 10.1016/j.archoralbio.2025.106401
Meiqing Wang , Dongmei He
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引用次数: 0
期刊
Archives of oral biology
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