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.
{"title":"Endoplasmic reticulum stress as a nexus of temporomandibular joint osteoarthritis","authors":"Xinqi Huang , Zinan Cen , Xinxuan Zhou , Zhihe Zhao , Xiao Cen","doi":"10.1016/j.archoralbio.2025.106407","DOIUrl":"10.1016/j.archoralbio.2025.106407","url":null,"abstract":"<div><h3>Objective</h3><div>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.</div></div><div><h3>Design</h3><div>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.</div></div><div><h3>Results</h3><div>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.</div></div><div><h3>Conclusions</h3><div>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.</div></div>","PeriodicalId":8288,"journal":{"name":"Archives of oral biology","volume":"180 ","pages":"Article 106407"},"PeriodicalIF":2.1,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145202279","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}
Pub Date : 2025-09-25DOI: 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.
{"title":"Antibacterial effects of charcoal and fluoride dentifrices in oral biofilms","authors":"Ashley N. Bowers , Caroline Coradi Tonon , Sam Yeo , Kinga Vojnits , Rayhan Shah , Sepideh Pakpour , Simone Duarte","doi":"10.1016/j.archoralbio.2025.106405","DOIUrl":"10.1016/j.archoralbio.2025.106405","url":null,"abstract":"<div><h3>Objectives</h3><div>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.</div></div><div><h3>Methods</h3><div>Biofilms of <em>Streptococcus mutans</em>, <em>S. gordonii</em>, and <em>S. sanguinis</em> 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.</div></div><div><h3>Results</h3><div>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 <em>S. gordonii</em>, and significantly reduced <em>S. mutans</em> and <em>S. sanguinis</em>. 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 > SnF<sub>2</sub>).</div></div><div><h3>Conclusions</h3><div>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.</div></div>","PeriodicalId":8288,"journal":{"name":"Archives of oral biology","volume":"180 ","pages":"Article 106405"},"PeriodicalIF":2.1,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145187910","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}
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.
{"title":"OIP5-AS1 expression profiles in different stages of oral squamous cell carcinoma","authors":"Ameya K.P., Ashikha Shirin Usman P.P., Durairaj Sekar","doi":"10.1016/j.archoralbio.2025.106403","DOIUrl":"10.1016/j.archoralbio.2025.106403","url":null,"abstract":"<div><h3>Objectives</h3><div>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.</div></div><div><h3>Design</h3><div>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).</div></div><div><h3>Results</h3><div>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.</div></div><div><h3>Conclusions</h3><div>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.</div></div>","PeriodicalId":8288,"journal":{"name":"Archives of oral biology","volume":"180 ","pages":"Article 106403"},"PeriodicalIF":2.1,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145156632","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}
Pub Date : 2025-09-24DOI: 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.
{"title":"Expression patterns of desmosome family members during tooth development and the role of Desmocollin-3 in cytodifferentiation of stratum intermedium","authors":"Triana Marchelina , Yuta Chiba , Shinji Otake , Li Wanshu , Hiroshi Sato , Yumiko Nakashima , Asuna Sugimoto , Tsutomu Iwamoto , Aya Yamada , Kan Saito , Satoshi Fukumoto","doi":"10.1016/j.archoralbio.2025.106404","DOIUrl":"10.1016/j.archoralbio.2025.106404","url":null,"abstract":"<div><h3>Objective</h3><div>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.</div></div><div><h3>Design</h3><div>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.</div></div><div><h3>Results</h3><div>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.</div></div><div><h3>Conclusion</h3><div>These findings indicate that Dsc3 is essential for SI structural integrity and its signaling support to ameloblasts.</div></div>","PeriodicalId":8288,"journal":{"name":"Archives of oral biology","volume":"180 ","pages":"Article 106404"},"PeriodicalIF":2.1,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145187867","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}
Pub Date : 2025-09-23DOI: 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.
{"title":"In Vitro antibacterial activity of Lactiplantibacillus sp. cell-free supernatants against Porphyromonas gingivalis: A potential approach for oral health","authors":"Hui Ying Yit , Zaleha Shafiei , Noraziah Mohamad Zin , Mazlina Mohd Said","doi":"10.1016/j.archoralbio.2025.106399","DOIUrl":"10.1016/j.archoralbio.2025.106399","url":null,"abstract":"<div><h3>Objective</h3><div>This study explores the potential of postbiotic metabolites from lactic acid bacteria (LAB) isolated from human milk and tempeh against <em>Porphyromonas gingivalis</em>, a key pathogen in periodontitis.</div></div><div><h3>Design</h3><div>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.</div></div><div><h3>Results</h3><div>Strain S2, a mixture of <em>Lactiplantibacillus</em> 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 <em>P. gingi</em>valis biofilm formation at a minimum concentration of 25 mg/mL, compared to the untreated control. Strain T2 was identified as <em>Lactiplantibacillus plantarum</em> using the API 50CHL test and 16S rDNA gene sequencing.</div></div><div><h3>Conclusion</h3><div>The combination metabolite S2 demonstrates promising inhibitory activity against <em>P. gingivalis</em> and may serve as an effective adjunctive therapy for periodontal infections, outperforming individual and other combination LAB strains tested.</div></div>","PeriodicalId":8288,"journal":{"name":"Archives of oral biology","volume":"180 ","pages":"Article 106399"},"PeriodicalIF":2.1,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145218424","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}
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.
{"title":"Molecular and thermal signatures of dental tissues in third molars: An in vitro comparative study using fourier-transform infrared spectroscopy and differential scanning calorimetry","authors":"Rola Zahedah , Recep Üstünsoy , Aliye Tuğçe Gürcan , Bircan Dinç","doi":"10.1016/j.archoralbio.2025.106402","DOIUrl":"10.1016/j.archoralbio.2025.106402","url":null,"abstract":"<div><h3>Objective</h3><div>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).</div></div><div><h3>Design</h3><div>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.</div></div><div><h3>Results</h3><div>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.</div></div><div><h3>Conclusion</h3><div>Molecular and thermal profiling of dental tissues provide baseline reference data for biomaterial design and regenerative strategies.</div></div><div><h3>Clinical significance</h3><div>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.</div></div>","PeriodicalId":8288,"journal":{"name":"Archives of oral biology","volume":"180 ","pages":"Article 106402"},"PeriodicalIF":2.1,"publicationDate":"2025-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145152422","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}
Pub Date : 2025-09-19DOI: 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.
{"title":"ZBP1-NLRP3 axis integrates PANoptosis and ferroptosis during inflammatory injury in human dental pulp fibroblasts","authors":"Ai-E. He , Xing Wang , Ni Xie, 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}
Pub Date : 2025-09-19DOI: 10.1016/j.archoralbio.2025.106401
Meiqing Wang , Dongmei He
{"title":"Editorial on the special issue on temporomandibular disorders (TMD), AOB journal","authors":"Meiqing Wang , Dongmei He","doi":"10.1016/j.archoralbio.2025.106401","DOIUrl":"10.1016/j.archoralbio.2025.106401","url":null,"abstract":"","PeriodicalId":8288,"journal":{"name":"Archives of oral biology","volume":"180 ","pages":"Article 106401"},"PeriodicalIF":2.1,"publicationDate":"2025-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145120437","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}
Pub Date : 2025-09-19DOI: 10.1016/j.archoralbio.2025.106400
Lilibeth-Stephania Escoto-Vasquez , Mario Alberto Alarcón-Sánchez , Julieta Sarai Becerra-Ruiz , Cristina Hermila Martínez-Bugarin , Sarah Monserrat Lomelí-Martínez , Armen A. Muradyan , Artak Heboyan
Objective
This project aimed to evaluate the immunoexpression pattern of murine double minute 2 (MDM2) in solid ameloblastomas compared to unicystic ameloblastomas.
Methods
The review followed PRISMA guidelines and was registered in the PROSPERO database. PubMed, Scopus, ScienceDirect, Web of Science, and Google Scholar were comprehensively searched. Original cross-sectional studies were included. The meta-analysis was performed using STATA V15 and RevMan. Positivity rates were pooled using a random-effects model (REM), the labeling index was analyzed using mean difference under a REM, and expression intensity (moderate–strong) was assessed as categorical data using a REM with Hartung-Knapp adjustment. Heterogeneity was evaluated with the Chi² test and I² statistic. The methodological quality and certainty of the evidence were assessed using the Joanna Briggs Institute items and the GRADE system.
Results
Nine studies (n = 438 specimens) were analyzed, of which 325/438 (74.2 %) were ameloblastoma biopsies. MDM2 positivity was detected in 403/438 cases (92 %). A statistically significant association in favor of solid ameloblastoma was observed (RR = 2.08; 95 %CI [1.66–2.60]; p = 0.005), indicating a twofold probability of finding high MDM2 expression in solid compared to unicystic ameloblastomas. Four of the nine studies (44.4 %) were considered to be of low quality, and the certainty of evidence was low to very low.
Conclusions
MDM2 expression was prevalent in both types of ameloblastomas, with a higher intensity of expression observed in solid cases. However, due to study heterogeneity, further investigations with more robust methodological designs are recommended to assess the diagnostic potential of MDM2 in ameloblastomas.
目的比较小鼠双分钟2 （MDM2）在实体型成釉细胞瘤和单囊型成釉细胞瘤中的免疫表达规律。方法该综述遵循PRISMA指南，并在PROSPERO数据库中注册。对PubMed、Scopus、ScienceDirect、Web of Science和b谷歌Scholar进行了全面检索。纳入了原始的横断面研究。meta分析采用STATA V15和RevMan进行。采用随机效应模型（REM）汇总阳性率，采用REM下的平均差值分析标记指数，采用Hartung-Knapp调整的REM作为分类数据评估表达强度（中-强）。采用Chi²检验和I²统计量评价异质性。使用乔安娜布里格斯研究所项目和GRADE系统评估方法质量和证据的确定性。结果共分析9份研究（n = 438份），其中325/438份（74.2 %）为成釉细胞瘤活检。MDM2阳性403/438例（92 %）。实体成釉细胞瘤与MDM2的相关性有统计学意义（RR = 2.08; 95 %CI [1.66-2.60]; p = 0.005），表明在实体成釉细胞瘤中发现MDM2高表达的概率是单囊性成釉细胞瘤的两倍。9项研究中有4项（44.4% %）被认为是低质量的，证据的确定性从低到非常低。结论smdm2在两种类型的成釉细胞瘤中均有表达，在实性病例中表达强度更高。然而，由于研究的异质性，建议采用更可靠的方法学设计进行进一步的研究，以评估MDM2在成釉细胞瘤中的诊断潜力。
{"title":"Immunohistochemical assessment of murine double minute 2 in solid vs unicystic ameloblastoma: A systematic review and meta-analysis","authors":"Lilibeth-Stephania Escoto-Vasquez , Mario Alberto Alarcón-Sánchez , Julieta Sarai Becerra-Ruiz , Cristina Hermila Martínez-Bugarin , Sarah Monserrat Lomelí-Martínez , Armen A. Muradyan , Artak Heboyan","doi":"10.1016/j.archoralbio.2025.106400","DOIUrl":"10.1016/j.archoralbio.2025.106400","url":null,"abstract":"<div><h3>Objective</h3><div>This project aimed to evaluate the immunoexpression pattern of murine double minute 2 (MDM2) in solid ameloblastomas compared to unicystic ameloblastomas.</div></div><div><h3>Methods</h3><div>The review followed PRISMA guidelines and was registered in the PROSPERO database. PubMed, Scopus, ScienceDirect, Web of Science, and Google Scholar were comprehensively searched. Original cross-sectional studies were included. The meta-analysis was performed using STATA V15 and RevMan. Positivity rates were pooled using a random-effects model (REM), the labeling index was analyzed using mean difference under a REM, and expression intensity (moderate–strong) was assessed as categorical data using a REM with Hartung-Knapp adjustment. Heterogeneity was evaluated with the Chi² test and I² statistic. The methodological quality and certainty of the evidence were assessed using the Joanna Briggs Institute items and the GRADE system.</div></div><div><h3>Results</h3><div>Nine studies (n = 438 specimens) were analyzed, of which 325/438 (74.2 %) were ameloblastoma biopsies. MDM2 positivity was detected in 403/438 cases (92 %). A statistically significant association in favor of solid ameloblastoma was observed (RR = 2.08; 95 %CI [1.66–2.60]; p = 0.005), indicating a twofold probability of finding high MDM2 expression in solid compared to unicystic ameloblastomas. Four of the nine studies (44.4 %) were considered to be of low quality, and the certainty of evidence was low to very low.</div></div><div><h3>Conclusions</h3><div>MDM2 expression was prevalent in both types of ameloblastomas, with a higher intensity of expression observed in solid cases. However, due to study heterogeneity, further investigations with more robust methodological designs are recommended to assess the diagnostic potential of MDM2 in ameloblastomas.</div></div>","PeriodicalId":8288,"journal":{"name":"Archives of oral biology","volume":"180 ","pages":"Article 106400"},"PeriodicalIF":2.1,"publicationDate":"2025-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145109677","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}
Pub Date : 2025-09-17DOI: 10.1016/j.archoralbio.2025.106397
Verônica Cabral dos Santos Cunha D'Assunção , Maria Heloísa de Souza Borges-Grisi , Isis Morais Bezerra Muniz , Francisco Naldo Gomes Filho , Camilla Freire de Brito Bastos , Luís Fellipe Alves Silva , Francisco Humberto Xavier-Júnior , Rodrigo Othávio de Assunção e Souza , Leopoldina de Fátima Dantas de Almeida
Objective
Evaluate the antimicrobial effect of an experimental mouthwash containing 1 % cinnamaldehyde in a polymicrobial biofilm model for peri-implant mucositis.
Materials and methods
Polymicrobial biofilms were seeded on zirconia and on titanium (n = 6 or 8/group) surfaces from stimulated saliva collection from 2 periodontal health donors and 2 with gingivitis. Salivary pellicle was performed, by 60 min. Inoculum was seeded (1 ×108 CFU/mL) in McBain medium (1 % of sucrose). Biofilms on zirconia were cultured in aerobiosis and on titanium in microaerophilic conditions for 24 h. Daily challenges with 10 % sucrose were stablished. Samples were exposed to the experimental mouthwash for 1 min, twice a day, for 72 h. Chlorhexidine digluconate at 0.12 % and saline solution (at 0.9 %) were used as controls. Biofilms were kept in culture for an additional 24 h to count viable cells, evaluate biomass and cellular metabolism.
Results
In zirconia, evaluation of cellular metabolism did not detect a statistically significant difference between the biofilm conditions (p > 0.05). It was found that cellular metabolism was decreased from exposure to mouthwash and chlorhexidine, with a difference compared to the negative control (p < 0.05). In titanium, viable cell count in two media and the biomass were higher for biofilms from the periodontal health salivary condition (p < 0.05). There was a decrease in the biomass of biofilms exposed to the experimental mouthwash for both salivary conditions. Metabolic activity was decreased when exposed to experimental mouthwash and chlorhexidine compared to the negative control (p < 0.05).
Conclusions
Experimental mouthwash with 1 % cinnamaldehyde showed an antimicrobial effect similar to chlorhexidine against polymicrobial biofilms.
{"title":"Antimicrobial effect of cinnamaldehyde in a peri-implant mucositis model","authors":"Verônica Cabral dos Santos Cunha D'Assunção , Maria Heloísa de Souza Borges-Grisi , Isis Morais Bezerra Muniz , Francisco Naldo Gomes Filho , Camilla Freire de Brito Bastos , Luís Fellipe Alves Silva , Francisco Humberto Xavier-Júnior , Rodrigo Othávio de Assunção e Souza , Leopoldina de Fátima Dantas de Almeida","doi":"10.1016/j.archoralbio.2025.106397","DOIUrl":"10.1016/j.archoralbio.2025.106397","url":null,"abstract":"<div><h3>Objective</h3><div>Evaluate the antimicrobial effect of an experimental mouthwash containing 1 % cinnamaldehyde in a polymicrobial biofilm model for peri-implant mucositis.</div></div><div><h3>Materials and methods</h3><div>Polymicrobial biofilms were seeded on zirconia and on titanium (n = 6 or 8/group) surfaces from stimulated saliva collection from 2 periodontal health donors and 2 with gingivitis. Salivary pellicle was performed, by 60 min. Inoculum was seeded (1 ×10<sup>8</sup> CFU/mL) in McBain medium (1 % of sucrose). Biofilms on zirconia were cultured in aerobiosis and on titanium in microaerophilic conditions for 24 h. Daily challenges with 10 % sucrose were stablished. Samples were exposed to the experimental mouthwash for 1 min, twice a day, for 72 h. Chlorhexidine digluconate at 0.12 % and saline solution (at 0.9 %) were used as controls. Biofilms were kept in culture for an additional 24 h to count viable cells, evaluate biomass and cellular metabolism.</div></div><div><h3>Results</h3><div>In zirconia, evaluation of cellular metabolism did not detect a statistically significant difference between the biofilm conditions (p > 0.05). It was found that cellular metabolism was decreased from exposure to mouthwash and chlorhexidine, with a difference compared to the negative control (p < 0.05). In titanium, viable cell count in two media and the biomass were higher for biofilms from the periodontal health salivary condition (p < 0.05). There was a decrease in the biomass of biofilms exposed to the experimental mouthwash for both salivary conditions. Metabolic activity was decreased when exposed to experimental mouthwash and chlorhexidine compared to the negative control (p < 0.05).</div></div><div><h3>Conclusions</h3><div>Experimental mouthwash with 1 % cinnamaldehyde showed an antimicrobial effect similar to chlorhexidine against polymicrobial biofilms.</div></div>","PeriodicalId":8288,"journal":{"name":"Archives of oral biology","volume":"179 ","pages":"Article 106397"},"PeriodicalIF":2.1,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145103173","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}
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