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Impact of stress on pain sensitization and emotional responses in a rat model of persistent TMJ inflammation 应激对持续性颞下颌关节炎症大鼠模型疼痛敏感性和情绪反应的影响
IF 2.1 4区 医学 Q2 DENTISTRY, ORAL SURGERY & MEDICINE Pub Date : 2025-11-19 DOI: 10.1016/j.archoralbio.2025.106463
Jardel Francisco Mazzi-Chaves , Ana Paula Ribeiro Novaes , Glauce Crivelaro Nascimento , Christie Ramos Andrade Leite-Panissi

Objective

Temporomandibular disorders (TMDs) are frequently associated with psychological distress, including anxiety and depression, which can modulate pain perception and sensitivity. This study investigated the impact of acute and chronic stress on the progression of temporomandibular joint (TMJ) pain, secondary hyperalgesia, and stress-induced affective disturbances.

Design

Using a well-established preclinical model, Wistar-Hannover rats underwent persistent TMJ inflammation via intra-articular administration of Freund’s complete adjuvant (CFA). Orofacial mechanical allodynia and secondary hyperalgesia were assessed using von Frey test in the orofacial region and hot plate test in the hind paw. To evaluate the influence of stress on affective behaviors, Acute stress (AS), chronic restraint stress (CRS) and Unpredictable chronic stress (UCS) paradigms were implemented, followed by behavioral assessments using the elevated plus maze (EPM), open field (OF), and sucrose preference tests.

Results

Results demonstrated that chronic stress exacerbated CFA-induced orofacial allodynia. TMJ inflammation induced secondary hyperalgesia, with AS partially restoring baseline nociception, while UCS amplified central sensitization. Notably, CRS did not influence hind paw nociception in CFA-injected rats. Behavioral analyses revealed that CFA injection heightened anxiety-like behavior by decreased open-arm exploration. Acute stress further intensified anxiety and impaired exploratory activity, whereas chronic stresses significantly worsened both anxiety- and depression-like behaviors.

Conclusion

These findings underscore the complex interplay between stress and pain processing in TMDs, highlighting the detrimental role of chronic stress in exacerbating pain sensitivity and emotional dysregulation. Understanding these mechanisms could lead to more effective, targeted treatments, improving patient outcomes.
目的颞下颌疾病(TMDs)常伴有焦虑、抑郁等心理困扰,可调节疼痛感知和敏感性。本研究探讨了急性和慢性应激对颞下颌关节(TMJ)疼痛、继发性痛觉过敏和应激性情感障碍进展的影响。设计采用成熟的临床前模型,Wistar-Hannover大鼠通过关节内给予Freund 's完全佐剂(CFA)进行持续性TMJ炎症。采用von Frey试验和后爪热板试验对大鼠口面部机械异常性痛和继发性痛觉过敏进行评估。为了评估应激对情感行为的影响,本研究采用急性应激(AS)、慢性约束应激(CRS)和不可预测慢性应激(UCS)范式,并采用升高+迷宫(EPM)、开阔场(of)和蔗糖偏好测试进行行为评估。结果慢性应激加重cfa诱导的口面部异常痛。颞下颌关节炎症引起继发性痛觉过敏,AS部分恢复基线痛觉,而UCS放大中枢致敏。值得注意的是,CRS对注射cfa的大鼠后爪痛觉没有影响。行为分析显示,CFA注射通过减少张开臂探查而增加焦虑样行为。急性应激进一步加剧了焦虑和探索性活动,而慢性应激显著恶化了焦虑和抑郁样行为。结论这些发现强调了应激与疼痛加工之间复杂的相互作用,强调了慢性应激在加剧疼痛敏感性和情绪失调中的有害作用。了解这些机制可以带来更有效、更有针对性的治疗,改善患者的预后。
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引用次数: 0
Growing new teeth: A systematic review of functional whole-tooth regeneration in orthotopic animal models 生长新牙:原位动物模型全牙功能再生的系统综述。
IF 2.1 4区 医学 Q2 DENTISTRY, ORAL SURGERY & MEDICINE Pub Date : 2025-11-15 DOI: 10.1016/j.archoralbio.2025.106461
Pei-Jung Wu, Mar Jovani-Sancho

Objective

To identify and evaluate current strategies for functional whole-tooth regeneration in orthotopic animal models with high translational potential.

Design

A systematic review of in vivo studies involving orthotopic implantation of generated tooth constructs, analyzing experimental design, cell sources, scaffolding materials, implantation techniques, and outcome measures including histological, radiological, and functional evaluations.

Results

Considerable heterogeneity was observed in animal models, developmental stages at implantation, and cellular components. Polycaprolactone (PCL) membranes were often associated with improved eruption and reduced ankylosis, suggesting enhanced periodontal integration.

Conclusions

PCL-based scaffolding systems may facilitate functional tooth regeneration, but further standardized in vivo research is needed to validate translational potential.
目的:确定和评估目前具有高转化潜力的原位动物模型的功能全牙再生策略。设计:系统回顾体内研究,包括生成的牙齿构建体的原位种植,分析实验设计、细胞来源、支架材料、种植技术和结果测量,包括组织学、放射学和功能评估。结果:在动物模型、着床发育阶段和细胞成分中观察到相当大的异质性。聚己内酯(PCL)膜通常与改善出疹和减少强直有关,表明牙周整合增强。结论:基于pcl的支架系统可能促进功能性牙齿再生,但需要进一步标准化的体内研究来验证其转化潜力。
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引用次数: 0
Tetramethoxyluteolin, an active constituent in mulberry leaves, promotes osteogenesis of jaw bone marrow mesenchymal stem cells in periodontitis microenvironment via NF-κB inhibition 桑叶中的活性成分四甲木犀草素通过抑制NF-κB促进牙周炎微环境下颌骨骨髓间充质干细胞成骨。
IF 2.1 4区 医学 Q2 DENTISTRY, ORAL SURGERY & MEDICINE Pub Date : 2025-11-15 DOI: 10.1016/j.archoralbio.2025.106459
Yuning Xia , Chao Shan , Zeyu Wu , Jin Zhao

Objective

This study aims to investigate the effects and mechanisms of tetramethoxyluteolin (TML), a bioactive compound in mulberry leaves, on jaw bone marrow mesenchymal stem cells (JBMMSCs) in a periodontitis microenvironment.

Design

Network pharmacology and molecular docking were used to identify mulberry leaves' active constituents and their targets in periodontitis treatment. An inflammatory model was established in JBMMSCs using Porphyromonas gingivalis-lipopolysaccharide (5 μg/mL). TML's optimal concentration was determined via CCK-8 and ELISA. Osteogenic differentiation, inflammatory markers, and NF-κB pathway activity were assessed using ALP/ARS staining, RT-PCR, and Western blot (WB). A rat model of ligature-induced periodontitis was established, and TML's effects were evaluated through histopathological staining, micro-CT, RT-PCR, and WB. JBMMSCs from each animal experimental group were isolated for in vitro osteogenic validation. Mechanisms were clarified by comparing TML with the NF-κB inhibitor BAY11–7082.

Results

TML was identified as the key constituent targeting NF-κB and inflammatory mediators (IL-6, IL-1β, TNF-α). 5 μM TML significantly suppressed inflammatory cytokines, promoted osteogenic differentiation, and inhibited NF-κB activation in JBMMSCs. In rats, 30 mg/kg TML markedly reduced inflammation and alveolar bone loss, showing efficacy comparable to indomethacin, and JBMMSCs from TML-treated groups exhibited enhanced osteogenesis. TML's inhibition of NF-κB was similar to BAY11–7082.

Conclusion

TML reduces periodontal inflammation and enhances the osteogenic potential of JBMMSCs by inhibiting the NF-κB pathway, providing a novel strategy for periodontitis-related bone regeneration.
目的:研究桑叶生物活性物质四甲木犀草素(TML)对牙周炎微环境下颌骨骨髓间充质干细胞(JBMMSCs)的影响及其机制。设计:采用网络药理学和分子对接的方法,鉴定桑叶的有效成分及其治疗牙周炎的靶点。采用牙龈卟啉单胞菌脂多糖(5 μg/mL)建立JBMMSCs炎症模型。通过CCK-8和ELISA法确定TML的最佳浓度。采用ALP/ARS染色、RT-PCR和Western blot (WB)检测成骨分化、炎症标志物和NF-κB通路活性。建立大鼠结扎性牙周炎模型,通过组织病理学染色、显微ct、RT-PCR和WB评价TML的作用。从每个动物实验组中分离JBMMSCs进行体外成骨验证。通过比较TML与NF-κB抑制剂BAY11-7082,阐明其作用机制。结果:TML是靶向NF-κB和炎症介质(IL-6、IL-1β、TNF-α)的关键成分。5 μM TML显著抑制JBMMSCs炎症因子,促进成骨分化,抑制NF-κB活化。在大鼠中,30 mg/kg TML显著减少炎症和牙槽骨丢失,其疗效与吲哚美辛相当,TML处理组的JBMMSCs表现出增强的成骨作用。TML对NF-κB的抑制作用与BAY11-7082相似。结论:TML通过抑制NF-κB通路,减轻牙周炎症,增强JBMMSCs成骨潜能,为牙周炎相关骨再生提供了一种新的策略。
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引用次数: 0
Is there geometric morphometric evidence for the selection against impaction? A comparative cross-sectional study of specific tooth-agenesis patterns 是否有几何形态计量学证据证明选择不受撞击?特定牙齿发育模式的比较横断面研究。
IF 2.1 4区 医学 Q2 DENTISTRY, ORAL SURGERY & MEDICINE Pub Date : 2025-11-15 DOI: 10.1016/j.archoralbio.2025.106462
Sarah Boussali , Anaïs Cavaré

Objectives

Reductions in tooth number and facial prognathism may reflect shared genetic and evolutionary mechanisms but have been inconsistently reported by traditional cephalometric analyses. This study aimed to assess whether common patterns of dental agenesis are associated with craniofacial morphology using geometric morphometric methods.

Design

This retrospective comparative cross-sectional study included 538 patients aged 10–19 years from a French orthodontic population. Individuals with hypodontia (n = 269), restricted to third molars, maxillary lateral incisors, or second premolars, were matched by age and sex with controls without agenesis (n = 269). Craniofacial morphology was assessed on lateral cephalograms using 18 landmarks and 87 semilandmarks. Multiple linear regression and Procrustes MANOVA were applied to evaluate differences in size and shape, adjusting for sex and age.

Results

No significant association was found between agenesis status and craniofacial size in the overall configuration as well as in the cranial base, maxilla, and mandible. A significant sex effect was detected in the mandible, with smaller centroid size in males (p = 0.012). Multivariate regression on shape confirmed allometric effects across all configurations. Procrustes MANOVA detected a significant effect of sex on overall shape (p = 0.003), but neither age nor hypodontia reached significance.

Conclusion

In this large geometric morphometric study, no generalized or localized alterations in craniofacial morphology were detected, even in third molar agenesis, suggesting that the anthropological significance of hypodontia should be regarded with caution.
目的:牙齿数量减少和面部前突可能反映了共同的遗传和进化机制,但传统的头颅测量分析报告不一致。本研究旨在利用几何形态计量学方法评估牙齿发育不全的常见模式是否与颅面形态相关。设计:这项回顾性比较横断面研究包括538名年龄在10-19岁的法国正畸人群。下颌缺失个体(n = 269),局限于第三磨牙,上颌侧门牙或第二前磨牙,按年龄和性别与无发育的对照组(n = 269)匹配。采用18个标志和87个半标志在侧位脑电图上评估颅面形态。应用多元线性回归和Procrustes方差分析评估大小和形状的差异,并对性别和年龄进行调整。结果:发育不全状态与颅面大小、颅底、上颌骨、下颌骨整体形态无显著相关性。下颌骨存在显著的性别效应,男性的质心尺寸较小(p = 0.012)。形状的多元回归证实了所有构型的异速生长效应。Procrustes MANOVA检测到性别对整体形状有显著影响(p = 0.003),但年龄和下颌畸形均无显著影响。结论:在这项大型几何形态测量学研究中,即使在第三磨牙发育中,也没有发现颅面形态的普遍或局部改变,这表明下颌畸形的人类学意义应该谨慎对待。
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引用次数: 0
Immunohistochemical analysis of immune checkpoint proteins (PD-1, PD-L1 and PD-L2) in giant cell granulomas of the jaws and giant cell tumor of bone 颌骨巨细胞肉芽肿和骨巨细胞瘤中免疫检查点蛋白PD-1、PD-L1和PD-L2的免疫组织化学分析。
IF 2.1 4区 医学 Q2 DENTISTRY, ORAL SURGERY & MEDICINE Pub Date : 2025-11-15 DOI: 10.1016/j.archoralbio.2025.106460
Elton Fernandes Barros , Vanessa Alves de Medeiros , Éricka Janine Dantas da Silveira , João Augusto Vianna Goulart Filho , Pollianna Muniz Alves , Cassiano Francisco Weege Nonaka

Objective

To evaluate the immunoexpression of programmed cell death protein 1 (PD-1) and programmed cell death ligands 1 (PD-L1) and 2 (PD-L2) in giant cell granulomas of the jaws (central giant cell granuloma [CGCG], peripheral giant cell granuloma [PGCG]) and giant cell tumor of bone (GCTB).

Design

Thirty CGCG (15 non-aggressive and 15 aggressive), 15 PGCG, and 15 GCTB were selected. The percentages of cytoplasmic (PD-1, PD-L1, and PD-L2) and nuclear (PD-L1) staining in mononuclear cells (MC) and in non-cannibalistic (ncMGC) and cannibalistic MGC (cMGC) were determined.

Results

Cytoplasmic expression of PD-1 and PD-L1 was observed in all groups, with high median percentages of positivity in ncMGC and cMGC. Compared to CGCG and PGCG, GCTB exhibited higher expression of PD-L1 in MC (p < 0.05). In ncMGC, expression of PD-1 was higher in GCTB compared to non-aggressive CGCG (p < 0.05). Similarly, higher PD-L1 immunopositivity was found in ncMGC of GCTB compared to aggressive CGCG and PGCG (p < 0.05). For all cell types, lower median percentages of PD-L2 positivity were observed in GCTB compared to CGCG and PGCG (p > 0.05). In GCTB, there was a strong positive correlation between the cytoplasmic expression of PD-L1 in MC and PD-1 in ncMGC (r = 0.535; p < 0.05). All groups exhibited low nuclear immunoexpression of PD-L1.

Conclusion

The results suggest the potential participation of PD-1, PD-L1, and PD-L2 in the pathogenesis of CGCG, PGCG, and GCTB. The locally aggressive behavior of GCTB could be associated with a higher osteoclastogenic and immunosuppressive microenvironment in these neoplasms.
目的:探讨程序性细胞死亡蛋白1 (PD-1)和程序性细胞死亡配体1 (PD-L1)、2 (PD-L2)在颌骨巨细胞肉芽肿(中央巨细胞肉芽肿[CGCG]、外周巨细胞肉芽肿[PGCG])和骨巨细胞瘤(GCTB)中的免疫表达。设计:选择30例CGCG(非侵袭性15例,侵袭性15例),PGCG 15例,GCTB 15例。测定单核细胞(MC)、非同类相食(ncMGC)和同类相食MGC (cMGC)细胞质(PD-1、PD-L1和PD-L2)和核(PD-L1)染色百分比。结果:PD-1和PD-L1在所有组的细胞质中均有表达,ncMGC和cMGC的中位阳性百分比较高。与CGCG和PGCG相比,GCTB在MC中的PD-L1表达更高(p  0.05)。在GCTB中,MC细胞质中PD-L1的表达与ncMGC中PD-1的表达呈正相关(r = 0.535;p )。结论:提示PD-1、PD-L1和PD-L2可能参与了CGCG、PGCG和GCTB的发病过程。GCTB的局部侵袭行为可能与这些肿瘤中较高的破骨细胞生成和免疫抑制微环境有关。
{"title":"Immunohistochemical analysis of immune checkpoint proteins (PD-1, PD-L1 and PD-L2) in giant cell granulomas of the jaws and giant cell tumor of bone","authors":"Elton Fernandes Barros ,&nbsp;Vanessa Alves de Medeiros ,&nbsp;Éricka Janine Dantas da Silveira ,&nbsp;João Augusto Vianna Goulart Filho ,&nbsp;Pollianna Muniz Alves ,&nbsp;Cassiano Francisco Weege Nonaka","doi":"10.1016/j.archoralbio.2025.106460","DOIUrl":"10.1016/j.archoralbio.2025.106460","url":null,"abstract":"<div><h3>Objective</h3><div>To evaluate the immunoexpression of programmed cell death protein 1 (PD-1) and programmed cell death ligands 1 (PD-L1) and 2 (PD-L2) in giant cell granulomas of the jaws (central giant cell granuloma [CGCG], peripheral giant cell granuloma [PGCG]) and giant cell tumor of bone (GCTB).</div></div><div><h3>Design</h3><div>Thirty CGCG (15 non-aggressive and 15 aggressive), 15 PGCG, and 15 GCTB were selected. The percentages of cytoplasmic (PD-1, PD-L1, and PD-L2) and nuclear (PD-L1) staining in mononuclear cells (MC) and in non-cannibalistic (ncMGC) and cannibalistic MGC (cMGC) were determined.</div></div><div><h3>Results</h3><div>Cytoplasmic expression of PD-1 and PD-L1 was observed in all groups, with high median percentages of positivity in ncMGC and cMGC. Compared to CGCG and PGCG, GCTB exhibited higher expression of PD-L1 in MC (<em>p</em> &lt; 0.05). In ncMGC, expression of PD-1 was higher in GCTB compared to non-aggressive CGCG (<em>p</em> &lt; 0.05). Similarly, higher PD-L1 immunopositivity was found in ncMGC of GCTB compared to aggressive CGCG and PGCG (<em>p</em> &lt; 0.05). For all cell types, lower median percentages of PD-L2 positivity were observed in GCTB compared to CGCG and PGCG (<em>p</em> &gt; 0.05). In GCTB, there was a strong positive correlation between the cytoplasmic expression of PD-L1 in MC and PD-1 in ncMGC (<em>r</em> = 0.535; <em>p</em> &lt; 0.05). All groups exhibited low nuclear immunoexpression of PD-L1.</div></div><div><h3>Conclusion</h3><div>The results suggest the potential participation of PD-1, PD-L1, and PD-L2 in the pathogenesis of CGCG, PGCG, and GCTB. The locally aggressive behavior of GCTB could be associated with a higher osteoclastogenic and immunosuppressive microenvironment in these neoplasms.</div></div>","PeriodicalId":8288,"journal":{"name":"Archives of oral biology","volume":"182 ","pages":"Article 106460"},"PeriodicalIF":2.1,"publicationDate":"2025-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145566592","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
RAW 264.7-derived exosomal miR-494–3p regulates inflammation and osteogenic differentiation of human periodontal ligament stem cells through regulating CAMK2D RAW 264.7衍生的外泌体miR-494-3p通过调节CAMK2D调节人牙周韧带干细胞的炎症和成骨分化
IF 2.1 4区 医学 Q2 DENTISTRY, ORAL SURGERY & MEDICINE Pub Date : 2025-11-11 DOI: 10.1016/j.archoralbio.2025.106457
Yue Zhang, Yufu Liang, Yue Zhou

Objective

This study aimed to investigate the effect of M2-exos on osteogenic differentiation in human periodontal ligament stem cells (hPDLSCs) and the underlying mechanism.

Design

Exosomes were isolated from M2-polarized RAW 264.7 macrophages and characterized by transmission electron microscopy, nanoparticle tracking analysis, and Western blot. hPDLSCs were treated with M2-exos, and osteogenic differentiation was assessed using alkaline phosphatase and Alizarin Red S staining, along with reverse transcription-quantitative polymerase chain reaction analysis of osteogenic markers. Inflammation-related cytokines were measured by enzyme-linked immunosorbent assay. Bioinformatics analysis identified miR-494–3p as a key miRNA in M2-exos, and its interaction with calcium/calmodulin-dependent protein kinase II delta (CAMK2D) was validated by RNA pull-down and dual luciferase reporter assays. Functional experiments were performed using a miR-494–3p inhibitor and CAMK2D knockdown in hPDLSCs.

Results

M2-exos exhibited typical exosomal characteristics and were internalized by hPDLSCs. Additionally, M2-exos suppressed inflammation and enhanced osteogenic differentiation. Mechanistically, miR-494–3p was highly enriched in M2-exos and directly targeted CAMK2D. Moreover, inhibition of miR-494–3p exacerbated inflammation and impaired osteogenesis, while CAMK2D knockdown reversed these effects, restoring osteogenic potential.

Conclusions

RAW 264.7-derived exosomes inhibited inflammation and promoted osteogenic differentiation in hPDLSCs, a process that involves, at least in part, the delivery of miR-494–3p. These findings highlight a novel mechanism and the therapeutic potential of targeting the miR-494–3p/CAMK2D axis in periodontal bone regeneration.
目的探讨M2-exos对人牙周韧带干细胞成骨分化的影响及其机制。design nexosomes从m2极化的RAW 264.7巨噬细胞中分离出来,并通过透射电子显微镜、纳米颗粒跟踪分析和Western blot对其进行了表征。用M2-exos处理hPDLSCs,用碱性磷酸酶和茜素红S染色评估成骨分化,并对成骨标志物进行逆转录-定量聚合酶链反应分析。采用酶联免疫吸附法检测炎症相关细胞因子。生物信息学分析发现miR-494-3p是M2-exos中的关键miRNA,并且通过RNA下拉和双荧光素酶报告基因试验验证了其与钙/钙调素依赖性蛋白激酶II δ (CAMK2D)的相互作用。在hPDLSCs中使用miR-494-3p抑制剂和CAMK2D敲低进行功能实验。结果sm2 -exos表现出典型的外泌体特征,并被hPDLSCs内化。此外,M2-exos抑制炎症并增强成骨分化。在机制上,miR-494-3p在M2-exos中高度富集,并直接靶向CAMK2D。此外,miR-494-3p的抑制加重了炎症和成骨损伤,而CAMK2D的敲低逆转了这些作用,恢复了成骨潜能。结论:raw264.7衍生的外泌体抑制hPDLSCs的炎症并促进成骨分化,这一过程至少部分涉及miR-494-3p的传递。这些发现强调了靶向miR-494-3p /CAMK2D轴在牙周骨再生中的新机制和治疗潜力。
{"title":"RAW 264.7-derived exosomal miR-494–3p regulates inflammation and osteogenic differentiation of human periodontal ligament stem cells through regulating CAMK2D","authors":"Yue Zhang,&nbsp;Yufu Liang,&nbsp;Yue Zhou","doi":"10.1016/j.archoralbio.2025.106457","DOIUrl":"10.1016/j.archoralbio.2025.106457","url":null,"abstract":"<div><h3>Objective</h3><div>This study aimed to investigate the effect of M2-exos on osteogenic differentiation in human periodontal ligament stem cells (hPDLSCs) and the underlying mechanism.</div></div><div><h3>Design</h3><div>Exosomes were isolated from M2-polarized RAW 264.7 macrophages and characterized by transmission electron microscopy, nanoparticle tracking analysis, and Western blot. hPDLSCs were treated with M2-exos, and osteogenic differentiation was assessed using alkaline phosphatase and Alizarin Red S staining, along with reverse transcription-quantitative polymerase chain reaction analysis of osteogenic markers. Inflammation-related cytokines were measured by enzyme-linked immunosorbent assay. Bioinformatics analysis identified miR-494–3p as a key miRNA in M2-exos, and its interaction with calcium/calmodulin-dependent protein kinase II delta (CAMK2D) was validated by RNA pull-down and dual luciferase reporter assays. Functional experiments were performed using a miR-494–3p inhibitor and CAMK2D knockdown in hPDLSCs.</div></div><div><h3>Results</h3><div>M2-exos exhibited typical exosomal characteristics and were internalized by hPDLSCs. Additionally, M2-exos suppressed inflammation and enhanced osteogenic differentiation. Mechanistically, miR-494–3p was highly enriched in M2-exos and directly targeted CAMK2D. Moreover, inhibition of miR-494–3p exacerbated inflammation and impaired osteogenesis, while CAMK2D knockdown reversed these effects, restoring osteogenic potential.</div></div><div><h3>Conclusions</h3><div>RAW 264.7-derived exosomes inhibited inflammation and promoted osteogenic differentiation in hPDLSCs, a process that involves, at least in part, the delivery of miR-494–3p. These findings highlight a novel mechanism and the therapeutic potential of targeting the miR-494–3p/CAMK2D axis in periodontal bone regeneration.</div></div>","PeriodicalId":8288,"journal":{"name":"Archives of oral biology","volume":"182 ","pages":"Article 106457"},"PeriodicalIF":2.1,"publicationDate":"2025-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145518981","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
In vivo immunological evaluation of indomethacin and omega-3 nanocapsules for the treatment of rheumatoid arthritis in the temporomandibular joints of rats 吲哚美辛和omega-3纳米胶囊治疗大鼠颞下颌关节类风湿关节炎的体内免疫学评价
IF 2.1 4区 医学 Q2 DENTISTRY, ORAL SURGERY & MEDICINE Pub Date : 2025-11-11 DOI: 10.1016/j.archoralbio.2025.106456
Victor Augusto Benedicto dos Santos , Francisco Carlos Groppo , Thomas Barbin , Adilson Sartoratto , Luiz Eduardo Nunes Ferreira , Michael Henrique Araujo Monteiro , Sidney Raimundo Figueroba

Objective

This study aimed to develop and characterize indomethacin nanocapsules with an omega-3 oily core and evaluate their potential for treating rheumatoid arthritis in rats, comparing their effects to free-form administration on cytokines IL-1β, IL-10, IL-6, and TNF-α in temporomandibular joint.

Design

Nanocapsules were synthesized with omega-3 as the oil phase containing indomethacin. They were characterized for mean hydrodynamic diameter, polydispersity index, zeta potential, morphology (TEM), encapsulation efficiency (HPLC), and cytotoxicity in RAW 264.7 macrophages (MTT assay). For in vivo evaluation, forty-eight adult male Wistar rats (n = 6) underwent rheumatoid arthritis induction via intradermal injection of Complete Freund's Adjuvant (CFA) and bovine type II collagen (CII) at the base of the tail. Rats were treated for 7 days by oral gavage with either nanocapsules (NC5, NC2.5), free indomethacin (IND5, IND2.5), or indomethacin combined with omega-3 (IND5 +ω3, IND2.5 +ω3). Cytokine levels in the temporomandibular joint were subsequently assessed.

Results

Nanocapsules displayed a spherical, well-defined morphology with diameters < 250 nm and exhibited lower cytotoxicity in RAW 264.7 cells compared to free-form treatments. In vivo, all treated groups showed significant reductions in IL-1β, IL-6, and TNF-α compared to the CFA group, along with a significant increase in IL-10.

Conclusions

Indomethacin nanocapsules with omega-3 effectively reduced pro-inflammatory cytokines and increased anti-inflammatory IL-10, demonstrating a superior immunomodulatory profile compared to free-form treatments.
本研究旨在开发和表征含有omega-3油芯的吲哚美辛纳米胶囊,并评估其治疗大鼠类风湿关节炎的潜力,比较其与自由给药对颞下颌关节细胞因子IL-1β、IL-10、IL-6和TNF-α的影响。设计以omega-3为油相,含吲哚美辛合成纳米胶囊。采用平均水动力直径、多分散性指数、zeta电位、形态(TEM)、包封效率(HPLC)和RAW 264.7巨噬细胞的细胞毒性(MTT法)对其进行表征。为了进行体内评估,48只成年雄性Wistar大鼠(n = 6)通过在尾巴底部皮内注射完全弗氏佐剂(CFA)和牛II型胶原(CII)诱导类风湿关节炎。大鼠分别口服纳米胶囊(NC5、NC2.5)、游离吲哚美辛(IND5、IND2.5)或吲哚美辛联合omega-3 (IND5 +ω3, IND2.5 +ω3)治疗7 d。随后评估了颞下颌关节的细胞因子水平。结果纳米胶囊呈球形,直径为<; 250 nm,在RAW 264.7细胞中表现出较低的细胞毒性。在体内,与CFA组相比,所有治疗组的IL-1β、IL-6和TNF-α水平均显著降低,IL-10水平显著升高。结论含omega-3的辛多美辛纳米胶囊可有效降低促炎细胞因子,增加抗炎IL-10,与自由形式的治疗相比,具有优越的免疫调节作用。
{"title":"In vivo immunological evaluation of indomethacin and omega-3 nanocapsules for the treatment of rheumatoid arthritis in the temporomandibular joints of rats","authors":"Victor Augusto Benedicto dos Santos ,&nbsp;Francisco Carlos Groppo ,&nbsp;Thomas Barbin ,&nbsp;Adilson Sartoratto ,&nbsp;Luiz Eduardo Nunes Ferreira ,&nbsp;Michael Henrique Araujo Monteiro ,&nbsp;Sidney Raimundo Figueroba","doi":"10.1016/j.archoralbio.2025.106456","DOIUrl":"10.1016/j.archoralbio.2025.106456","url":null,"abstract":"<div><h3>Objective</h3><div>This study aimed to develop and characterize indomethacin nanocapsules with an omega-3 oily core and evaluate their potential for treating rheumatoid arthritis in rats, comparing their effects to free-form administration on cytokines IL-1β, IL-10, IL-6, and TNF-α in temporomandibular joint.</div></div><div><h3>Design</h3><div>Nanocapsules were synthesized with omega-3 as the oil phase containing indomethacin. They were characterized for mean hydrodynamic diameter, polydispersity index, zeta potential, morphology (TEM), encapsulation efficiency (HPLC), and cytotoxicity in RAW 264.7 macrophages (MTT assay). For in vivo evaluation, forty-eight adult male Wistar rats (n = 6) underwent rheumatoid arthritis induction via intradermal injection of Complete Freund's Adjuvant (CFA) and bovine type II collagen (CII) at the base of the tail. Rats were treated for 7 days by oral gavage with either nanocapsules (NC5, NC2.5), free indomethacin (IND5, IND2.5), or indomethacin combined with omega-3 (IND5 +ω3, IND2.5 +ω3). Cytokine levels in the temporomandibular joint were subsequently assessed.</div></div><div><h3>Results</h3><div>Nanocapsules displayed a spherical, well-defined morphology with diameters &lt; 250 nm and exhibited lower cytotoxicity in RAW 264.7 cells compared to free-form treatments. In vivo, all treated groups showed significant reductions in IL-1β, IL-6, and TNF-α compared to the CFA group, along with a significant increase in IL-10.</div></div><div><h3>Conclusions</h3><div>Indomethacin nanocapsules with omega-3 effectively reduced pro-inflammatory cytokines and increased anti-inflammatory IL-10, demonstrating a superior immunomodulatory profile compared to free-form treatments.</div></div>","PeriodicalId":8288,"journal":{"name":"Archives of oral biology","volume":"182 ","pages":"Article 106456"},"PeriodicalIF":2.1,"publicationDate":"2025-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145518983","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
Effects of Bifidobacterium longum, Lactobacillus rhamnosus, and Lactobacillus reuteri on oral microbial balance and host cell functions: Implications for the prevention and management of oral diseases 长双歧杆菌、鼠李糖乳杆菌和罗伊氏乳杆菌对口腔微生物平衡和宿主细胞功能的影响:对口腔疾病预防和管理的影响
IF 2.1 4区 医学 Q2 DENTISTRY, ORAL SURGERY & MEDICINE Pub Date : 2025-11-11 DOI: 10.1016/j.archoralbio.2025.106458
Zhigang Zhu , Xiang Li , Jianwei Liu , Liang Chen , Yutong Zhan , Li Wang , Luxian Zhou , Dandan Jiang , Xianwu Peng , Xiuyu Jiang

Objectives

This study aimed to evaluate the effects of three probiotic samples—Bifidobacterium longum, Lactobacillus rhamnosus, and Lactobacillus reuteri—on oral pathogens, commensal bacteria, and host oral cells, thereby exploring their potential roles in maintaining microbial balance and promoting host defense.

Design

Probiotic culture supernatants (postbiotic fractions) were tested against oral pathogens (S. mutans, P. gingivalis, F. nucleatum, A. actinomycetemcomitans) and commensal species (S. sanguinis, V. parvula) using optical density assays. Primary human gingival fibroblasts and oral keratinocytes were co-cultured with probiotic preparations to assess cell viability, inflammatory cytokine secretion, and barrier gene expression (FLG, LOR).

Results

B. longum, L. rhamnosus, and L. reuteri samples showed strain- and concentration-dependent inhibition of oral pathogens, while exhibiting minimal effects on beneficial commensals. Appropriate concentrations of probiotic samples preserved fibroblast viability and enhanced keratinocyte survival. Notably, B. longum, L. rhamnosus, and L. reuteri upregulated barrier-associated genes (FLG, LOR) and suppressed IL-6 secretion in inflamed keratinocytes, suggesting immunomodulatory and protective roles.

Conclusions

Probiotic-derived metabolites exert selective antimicrobial and cytoprotective effects in the oral microenvironment. These findings support the dual functions of probiotics in reshaping oral microbial balance and modulating host cell functions and highlight the potential for personalized probiotic strategies in oral disease prevention and management.Further exploration of combined probiotic formulations is warranted to optimize clinical translation.
目的研究长双歧杆菌、鼠李糖乳杆菌和罗伊氏乳杆菌三种益生菌样品对口腔病原菌、共生菌和宿主口腔细胞的影响,探讨其在维持微生物平衡和促进宿主防御方面的潜在作用。设计采用光密度法检测益生菌培养上清液(生后组分)对口腔病原菌(变形链球菌、牙龈卟啉卟啉链球菌、核核卟啉卟啉卟啉链球菌、放线菌卟啉卟啉链球菌)和共生菌(血源性卟啉链球菌、细小弧菌)的抑制作用。用益生菌制剂对原代人牙龈成纤维细胞和口腔角化细胞进行共培养,观察细胞活力、炎性细胞因子分泌和屏障基因表达(FLG, LOR)。龙舌兰、鼠李糖乳杆菌和罗伊氏乳杆菌样品显示出菌株和浓度依赖性的口腔病原体抑制,而对有益共生菌的影响最小。适当浓度的益生菌样品可以保存成纤维细胞的活力,提高角质细胞的存活率。值得注意的是,长芽孢杆菌、鼠李糖乳杆菌和罗伊氏乳杆菌上调了屏障相关基因(FLG、LOR),抑制了炎症角质形成细胞中IL-6的分泌,提示其具有免疫调节和保护作用。结论益生菌衍生代谢物在口腔微环境中具有选择性抗菌和细胞保护作用。这些发现支持了益生菌在重塑口腔微生物平衡和调节宿主细胞功能方面的双重功能,并强调了个性化益生菌在口腔疾病预防和管理中的潜力。进一步探索联合益生菌制剂是必要的,以优化临床转化。
{"title":"Effects of Bifidobacterium longum, Lactobacillus rhamnosus, and Lactobacillus reuteri on oral microbial balance and host cell functions: Implications for the prevention and management of oral diseases","authors":"Zhigang Zhu ,&nbsp;Xiang Li ,&nbsp;Jianwei Liu ,&nbsp;Liang Chen ,&nbsp;Yutong Zhan ,&nbsp;Li Wang ,&nbsp;Luxian Zhou ,&nbsp;Dandan Jiang ,&nbsp;Xianwu Peng ,&nbsp;Xiuyu Jiang","doi":"10.1016/j.archoralbio.2025.106458","DOIUrl":"10.1016/j.archoralbio.2025.106458","url":null,"abstract":"<div><h3>Objectives</h3><div>This study aimed to evaluate the effects of three probiotic samples—<em>Bifidobacterium longum</em>, <em>Lactobacillus rhamnosus</em>, and <em>Lactobacillus reuteri</em>—on oral pathogens, commensal bacteria, and host oral cells, thereby exploring their potential roles in maintaining microbial balance and promoting host defense.</div></div><div><h3>Design</h3><div>Probiotic culture supernatants (postbiotic fractions) were tested against oral pathogens (<em>S. mutans</em>, <em>P. gingivalis</em>, <em>F. nucleatum</em>, <em>A. actinomycetemcomitans</em>) and commensal species (<em>S. sanguinis</em>, <em>V. parvula</em>) using optical density assays. Primary human gingival fibroblasts and oral keratinocytes were co-cultured with probiotic preparations to assess cell viability, inflammatory cytokine secretion, and barrier gene expression (<em>FLG</em>, <em>LOR</em>).</div></div><div><h3>Results</h3><div><em>B. longum, L. rhamnosus, and L. reuteri</em> samples showed strain- and concentration-dependent inhibition of oral pathogens, while exhibiting minimal effects on beneficial commensals. Appropriate concentrations of probiotic samples preserved fibroblast viability and enhanced keratinocyte survival. Notably, <em>B. longum</em>, <em>L. rhamnosus</em>, and <em>L. reuteri</em> upregulated barrier-associated genes (<em>FLG</em>, <em>LOR</em>) and suppressed IL-6 secretion in inflamed keratinocytes, suggesting immunomodulatory and protective roles.</div></div><div><h3>Conclusions</h3><div>Probiotic-derived metabolites exert selective antimicrobial and cytoprotective effects in the oral microenvironment. These findings support the dual functions of probiotics in reshaping oral microbial balance and modulating host cell functions and highlight the potential for personalized probiotic strategies in oral disease prevention and management.Further exploration of combined probiotic formulations is warranted to optimize clinical translation.</div></div>","PeriodicalId":8288,"journal":{"name":"Archives of oral biology","volume":"182 ","pages":"Article 106458"},"PeriodicalIF":2.1,"publicationDate":"2025-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145577799","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
Biomechanical impact of tooth root morphology to inform dental implant design 牙根形态对种植体设计的生物力学影响。
IF 2.1 4区 医学 Q2 DENTISTRY, ORAL SURGERY & MEDICINE Pub Date : 2025-11-09 DOI: 10.1016/j.archoralbio.2025.106455
Amber P. Wood-Bailey , Chris Smith , Laura C. Fitton , Alana C. Sharp

Objective

Using finite element analysis (FEA), this study aims to investigate the impact of different tooth root morphologies and implant designs, including a standard implant and a custom root-analogue implant on stress and strain distribution across the mandible.

Design

Six models were created by varying the root morphology of one tooth (the mandibular first molar) under identical loading scenarios: an original molar root, an incisor root, a canine root, a taurodont root, a standard implant, and a custom root-analogue implant replicating the original root morphology.

Results

Models with the original molar and custom implant exhibited similar stress and strain distributions over the mandible and had higher principal strains (tensile and compressive) compared to the single-rooted and standard implant models. Specifically, the maximum tensile and compressive strain values in the mandible of the custom implant model reach 94.89 % and 99.15 % of those in the original tooth root model. In contrast, the other models show less than 55.68 % similarity.

Conclusions

Custom root-analogue implants, which mimic natural root morphology, demonstrated more favourable stress distribution patterns, similar to those of the natural molar, compared to single-root implants. Our findings suggest that multi-rooted teeth are biomechanically optimized for dissipating masticatory loads, and standard single-root implants may not adequately replicate these properties, leading to poor load distribution and increased failure risk in posterior locations. Further research is needed to refine custom root-analogue implant designs and optimize their clinical application to better match the natural biomechanical environment of the maxilla and mandible.
目的:采用有限元分析(FEA),研究不同牙根形态和种植体设计对下颌骨应力应变分布的影响,包括标准种植体和定制模拟牙根种植体。设计:通过改变一颗牙齿(下颌第一磨牙)在相同加载情景下的牙根形态,创建了6个模型:原始磨牙根、门牙根、犬牙根、牛头齿根、标准种植体和复制原始牙根形态的定制牙根模拟种植体。结果:与单根和标准种植体模型相比,原始磨牙和定制种植体模型在下颌骨上表现出相似的应力和应变分布,并且具有更高的主应变(拉伸和压缩)。其中,定制种植体模型下颌骨的最大拉伸应变和最大压缩应变分别达到原牙根模型的94.89 %和99.15 %。相比之下,其他模型的相似度小于55.68 %。结论:与单根种植体相比,模拟天然根形态的定制根模拟种植体表现出与天然磨牙相似的更有利的应力分布模式。我们的研究结果表明,多根牙在生物力学上优化了咀嚼负荷的消散,而标准的单根种植体可能无法充分复制这些特性,导致负荷分布不佳,增加了后牙位置失败的风险。需要进一步的研究来完善定制的根模拟种植体设计并优化其临床应用,以更好地匹配上下颌骨的自然生物力学环境。
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引用次数: 0
Effect of high-lipid environment on human gingival fibroblast on titanium surface: An in-vitro study 高脂环境对钛表面人牙龈成纤维细胞影响的体外研究
IF 2.1 4区 医学 Q2 DENTISTRY, ORAL SURGERY & MEDICINE Pub Date : 2025-11-07 DOI: 10.1016/j.archoralbio.2025.106454
Shuyi Tan, Maoquan Li, Zhiqiang Liu, Aijie Chen, Jialing Wu, Ruiqi Li, Xiachen Li, Shuangquan Wan

Objectives

Hyperlipidemia is associated with dental peri-implantitis. Long-term success of dental implant relies on good peri-implant soft tissue barrier. This study aims to investigate the effect of high-lipid environment on biological activities of gingival fibroblast on titanium surface so as to explore the effect of hyperlipidemia on peri-implant soft tissue.

Design

Human gingival fibroblast-1(HGF-1) was seeded on the titanium surfaces and cultured in normal and high-lipid culture medium for 4 days. Cell adhesion and proliferation were assessed by cell counting and morphological observation following fluorescent staining. RNA sequencing were performed afterwards, followed by differentially expressed genes analysis, several enrichment analyses and Protein-Protein Interaction (PPI) analysis.

Results

The number of HGF-1 cells significantly decreased and the morphology of HGF-1 changed in high-lipid culture environment. Moreover, the expression levels of several hub genes, including Interleukin-6 (IL-6), C-X-C motif chemokine ligand 8 (CXCL8), and Activating Transcription Factor 3 (ATF3), as well as the activity of pathways such as the IL-17 signaling pathway and nuclear factor kappa-B (NF-κB) signaling pathway, were elevated. Meanwhile, the down-regulation of cell proliferation activities, like DNA replication and cell division was also observed.

Conclusions

High-lipid environment impaired the adhesion and proliferation of HGF-1 on titanium surface, which may be associated with the upregulation of specific genes and pathways, alongside the downregulation of cell proliferation-related activities.
目的:高脂血症与牙体种植周炎相关。种植体的长期成功依赖于良好的种植体周围软组织屏障。本研究旨在通过研究高脂环境对钛表面牙龈成纤维细胞生物活性的影响,探讨高脂血症对种植体周围软组织的影响。设计将人牙龈成纤维细胞-1(HGF-1)接种于钛表面,在正常和高脂培养基中培养4天。荧光染色后通过细胞计数和形态学观察观察细胞粘附和增殖情况。随后进行RNA测序,然后进行差异表达基因分析,一些富集分析和蛋白质-蛋白质相互作用(PPI)分析。结果在高脂培养环境下,HGF-1细胞数量明显减少,HGF-1形态发生改变。此外,白细胞介素-6 (IL-6)、C-X-C基序趋化因子配体8 (CXCL8)、活化转录因子3 (ATF3)等中心基因的表达水平以及IL-17信号通路、核因子κ b (NF-κB)信号通路的活性均升高。同时,DNA复制和细胞分裂等细胞增殖活性也出现下调。结论高脂环境抑制HGF-1在钛表面的粘附和增殖,其机制可能与特定基因和通路的上调有关,同时下调细胞增殖相关活性。
{"title":"Effect of high-lipid environment on human gingival fibroblast on titanium surface: An in-vitro study","authors":"Shuyi Tan,&nbsp;Maoquan Li,&nbsp;Zhiqiang Liu,&nbsp;Aijie Chen,&nbsp;Jialing Wu,&nbsp;Ruiqi Li,&nbsp;Xiachen Li,&nbsp;Shuangquan Wan","doi":"10.1016/j.archoralbio.2025.106454","DOIUrl":"10.1016/j.archoralbio.2025.106454","url":null,"abstract":"<div><h3>Objectives</h3><div>Hyperlipidemia is associated with dental peri-implantitis. Long-term success of dental implant relies on good peri-implant soft tissue barrier. This study aims to investigate the effect of high-lipid environment on biological activities of gingival fibroblast on titanium surface so as to explore the effect of hyperlipidemia on peri-implant soft tissue.</div></div><div><h3>Design</h3><div>Human gingival fibroblast-1(HGF-1) was seeded on the titanium surfaces and cultured in normal and high-lipid culture medium for 4 days. Cell adhesion and proliferation were assessed by cell counting and morphological observation following fluorescent staining. RNA sequencing were performed afterwards, followed by differentially expressed genes analysis, several enrichment analyses and Protein-Protein Interaction (PPI) analysis.</div></div><div><h3>Results</h3><div>The number of HGF-1 cells significantly decreased and the morphology of HGF-1 changed in high-lipid culture environment. Moreover, the expression levels of several hub genes, including Interleukin-6 (IL-6), C-X-C motif chemokine ligand 8 (CXCL8), and Activating Transcription Factor 3 (ATF3), as well as the activity of pathways such as the IL-17 signaling pathway and nuclear factor kappa-B (NF-κB) signaling pathway, were elevated. Meanwhile, the down-regulation of cell proliferation activities, like DNA replication and cell division was also observed.</div></div><div><h3>Conclusions</h3><div>High-lipid environment impaired the adhesion and proliferation of HGF-1 on titanium surface, which may be associated with the upregulation of specific genes and pathways, alongside the downregulation of cell proliferation-related activities.</div></div>","PeriodicalId":8288,"journal":{"name":"Archives of oral biology","volume":"182 ","pages":"Article 106454"},"PeriodicalIF":2.1,"publicationDate":"2025-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145500258","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
期刊
Archives of oral biology
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