Pub Date : 2025-12-09DOI: 10.1016/j.archoralbio.2025.106478
Mukarramah Zainal , Nurul ‘Izzah Mohd Sarmin , Mohammad Johari Ibrahim , Nicola Cirillo , Stuart G. Dashper , Mohd Hafiz Arzmi
Objectives
This study aims to determine the paracrine effects of Candida auris phenotypic switching in mono- and co-culture with Staphylococcus aureus on oral epithelial homeostasis and oncogenic progression in phenotypically normal (hTERT TIGKs) and malignant (ORL-48) oral keratinocytes.
Design
C. auris switched phenotype was scored using Phloxine B, and mono- and co-culture biofilms with S. aureus were developed. hTERT TIGKs and ORL-48 cell lines were independently seeded into 6-well and 96-well plates for dispase and viability test, respectively. The oral cell lines were exposed to phenotypically switched C. auris mono- and co-culture biofilm test cell growth medium (TCGM) for 24 h. Outcomes included cell morphology, metabolic activity/viability (CCK-8), and cell–cell adhesion (dispase assay).
Results
Microscopic observation revealed that the biofilm induced damage and disrupted epithelial cell integrity in a paracrine manner. The mono- and co-culture TCGM suppressed the growth of normal cells while promoting the metabolic activity of cancer cells. The adhesion analysis of hTERT TIGKs indicated a strong intercellular cohesion, while ORL-48 cells downregulated intercellular adhesion and compromised cell-cell cohesion.
Conclusion
C. auris biofilms promote the development of a malignant phenotype by regulating cell viability, promoting epithelial-mesenchymal transition, and adhesion in a switched generation-dependent manner.
{"title":"Effect of phenotype switched Candida auris mono-culture and co-culture biofilms on the morphology, viability, and adhesion of hTERT TIGKs and ORL-48 cell lines","authors":"Mukarramah Zainal , Nurul ‘Izzah Mohd Sarmin , Mohammad Johari Ibrahim , Nicola Cirillo , Stuart G. Dashper , Mohd Hafiz Arzmi","doi":"10.1016/j.archoralbio.2025.106478","DOIUrl":"10.1016/j.archoralbio.2025.106478","url":null,"abstract":"<div><h3>Objectives</h3><div>This study aims to determine the paracrine effects of <em>Candida auris</em> phenotypic switching in mono- and co-culture with <em>Staphylococcus aureus</em> on oral epithelial homeostasis and oncogenic progression in phenotypically normal (hTERT TIGKs) and malignant (ORL-48) oral keratinocytes.</div></div><div><h3>Design</h3><div><em>C. auris</em> switched phenotype was scored using Phloxine B, and mono- and co-culture biofilms with <em>S. aureus</em> were developed. hTERT TIGKs and ORL-48 cell lines were independently seeded into 6-well and 96-well plates for dispase and viability test, respectively. The oral cell lines were exposed to phenotypically switched <em>C. auris</em> mono- and co-culture biofilm test cell growth medium (TCGM) for 24 h. Outcomes included cell morphology, metabolic activity/viability (CCK-8), and cell–cell adhesion (dispase assay).</div></div><div><h3>Results</h3><div>Microscopic observation revealed that the biofilm induced damage and disrupted epithelial cell integrity in a paracrine manner. The mono- and co-culture TCGM suppressed the growth of normal cells while promoting the metabolic activity of cancer cells. The adhesion analysis of hTERT TIGKs indicated a strong intercellular cohesion, while ORL-48 cells downregulated intercellular adhesion and compromised cell-cell cohesion.</div></div><div><h3>Conclusion</h3><div><em>C. auris</em> biofilms promote the development of a malignant phenotype by regulating cell viability, promoting epithelial-mesenchymal transition, and adhesion in a switched generation-dependent manner.</div></div>","PeriodicalId":8288,"journal":{"name":"Archives of oral biology","volume":"182 ","pages":"Article 106478"},"PeriodicalIF":2.1,"publicationDate":"2025-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145783979","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 : 2025-12-04DOI: 10.1016/j.archoralbio.2025.106467
Da-In Choi , Hyun-Ji Kim , Dong-Guk Park , Jae-Han Lee , Thantrira Porntaveetus , Sung-Dae Cho
Objectives
BBI608 has demonstrated antitumor activity in several human cancers. However, its efficacy against mucoepidermoid carcinoma (MEC) remains unexplored. This study investigated the antitumor potential of BBI608 in MEC cell lines.
Design
The antitumor activity of BBI608 in MC3 and YD-15 mucoepidermoid carcinoma (MEC) cell lines was assessed using trypan blue exclusion, Live/Dead, and sphere formation assays. Apoptotic effects were investigated via western blotting, 4′,6-diamidino-2-phenylindole (DAPI) staining, Annexin V-fluorescein isothiocyanate/propidium iodide (V-FITC/PI) double staining, and reverse transcription-quantitative PCR.
Results
BBI608 exhibited growth-inhibitory effects in MEC cell lines, decreasing cell viability and sphere formation capacity while increasing cell death. BBI608-induced apoptosis was confirmed by increased cleaved caspase-3 and PARP expression, nuclear morphological changes characteristic of apoptosis, and increased Annexin V positivity. Furthermore, BBI608 significantly downregulated Mcl-1 expression, which contributed to apoptosis induction in MEC cells. This Mcl-1 downregulation appeared to be mediated by both proteasome-dependent protein degradation and translational regulatory mechanisms in MC3 and YD-15 cells, respectively.
Conclusion
These findings demonstrate that BBI608 effectively inhibits MEC cell proliferation in vitro by inducing Mcl-1-dependent apoptosis. This suggests BBI608 warrants further investigation as a potential therapeutic agent for MEC.
{"title":"BBI608 induces apoptosis in mucoepidermoid carcinoma cells by targeting a post-transcriptional regulatory mechanisms of myeloid cell leukemia-1","authors":"Da-In Choi , Hyun-Ji Kim , Dong-Guk Park , Jae-Han Lee , Thantrira Porntaveetus , Sung-Dae Cho","doi":"10.1016/j.archoralbio.2025.106467","DOIUrl":"10.1016/j.archoralbio.2025.106467","url":null,"abstract":"<div><h3>Objectives</h3><div>BBI608 has demonstrated antitumor activity in several human cancers. However, its efficacy against mucoepidermoid carcinoma (MEC) remains unexplored. This study investigated the antitumor potential of BBI608 in MEC cell lines.</div></div><div><h3>Design</h3><div>The antitumor activity of BBI608 in MC3 and YD-15 mucoepidermoid carcinoma (MEC) cell lines was assessed using trypan blue exclusion, Live/Dead, and sphere formation assays. Apoptotic effects were investigated via western blotting, 4′,6-diamidino-2-phenylindole (DAPI) staining, Annexin V-fluorescein isothiocyanate/propidium iodide (V-FITC/PI) double staining, and reverse transcription-quantitative PCR.</div></div><div><h3>Results</h3><div>BBI608 exhibited growth-inhibitory effects in MEC cell lines, decreasing cell viability and sphere formation capacity while increasing cell death. BBI608-induced apoptosis was confirmed by increased cleaved caspase-3 and PARP expression, nuclear morphological changes characteristic of apoptosis, and increased Annexin V positivity. Furthermore, BBI608 significantly downregulated Mcl-1 expression, which contributed to apoptosis induction in MEC cells. This Mcl-1 downregulation appeared to be mediated by both proteasome-dependent protein degradation and translational regulatory mechanisms in MC3 and YD-15 cells, respectively.</div></div><div><h3>Conclusion</h3><div>These findings demonstrate that BBI608 effectively inhibits MEC cell proliferation in vitro by inducing Mcl-1-dependent apoptosis. This suggests BBI608 warrants further investigation as a potential therapeutic agent for MEC.</div></div>","PeriodicalId":8288,"journal":{"name":"Archives of oral biology","volume":"182 ","pages":"Article 106467"},"PeriodicalIF":2.1,"publicationDate":"2025-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145681572","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}
In many jurisdictions, the 14-year threshold is a legally significant factor in determining criminal responsibility and related decisions. We investigated whether third-molar agenesis is associated with differences in the mineralisation stage of the mandibular second molar in South Indian children.
Design
Orthopantomograms from 570 children (240 males, 330 females; 10–14.99 years) were staged using Demirjian A to H criteria. Descriptive comparisons were supplemented with a proportional-odds ordinal logistic regression, modelling second-molar stage as the ordered outcome, with agenesis extent, age, and sex as predictors. Results are reported as adjusted odds ratios (aORs).
Results
Each additional year of age was associated with substantially higher odds of being in a more advanced second-molar stage (aOR 5.41, 95 % CI 4.47–6.56). Males had lower odds than females of being in a higher stage (aOR 0.58, 95 % CI 0.41–0.81). Relative to children with no third-molar agenesis, the odds of being in a higher second-molar stage were progressively lower with greater agenesis: one missing (aOR 0.53, 95 % CI 0.31–0.91), two missing (aOR 0.39, 95 % CI 0.24–0.62), three missing (aOR 0.26, 95 % CI 0.11–0.62), and all four missing (aOR 0.04, 95 % CI 0.02–0.09).
Conclusion
Third-molar agenesis was associated with less advanced mandibular second-molar stages after accounting for age and sex. Agenesis status and extent may be relevant for the 14-year threshold. Future work should develop and externally validate prediction models that integrate third molar agenesis to improve accuracy and minimise misclassification.
背景与目的在许多司法管辖区,14年刑期是确定刑事责任和相关决定的重要法律因素。我们研究了南印度儿童下颌第二磨牙矿化阶段的差异是否与第三磨牙发育不全有关。设计采用Demirjian A - H标准对570名儿童(男240名,女330名,10-14.99岁)进行骨断层扫描。描述性比较补充了比例-几率有序逻辑回归,将第二磨牙期建模为有序结果,以发育程度、年龄和性别为预测因子。结果以调整优势比(aORs)报告。结果每增加一岁,出现第二磨牙期晚期的几率显著增加(aOR 5.41, 95 % CI 4.47-6.56)。男性处于较高阶段的几率低于女性(aOR 0.58, 95 % CI 0.41-0.81)。相对于没有第三磨牙发育不全的儿童,第二磨牙发育期较高的几率随着发育不全逐渐降低:1个缺失(aOR 0.53, 95 % CI 0.31-0.91), 2个缺失(aOR 0.39, 95 % CI 0.24-0.62), 3个缺失(aOR 0.26, 95 % CI 0.11-0.62), 4个缺失(aOR 0.04, 95 % CI 0.02-0.09)。结论考虑年龄和性别因素后,下颌第三磨牙发育不全与下颌第二磨牙发育较晚有关。发育状态和程度可能与14岁的阈值有关。未来的工作应该开发和外部验证整合第三磨牙发育的预测模型,以提高准确性和减少错误分类。
{"title":"Third-molar agenesis shifts mandibular second-molar mineralisation timeline: An orthopantomographic study in South Indian children","authors":"Subramanyeswara Swamy Chinni , Nallan CSK Chaitanya , Waheeda Shahnaz , Usha Gangavarapu , Shivani Ramesh Mungala , Sudheer B. Balla","doi":"10.1016/j.archoralbio.2025.106466","DOIUrl":"10.1016/j.archoralbio.2025.106466","url":null,"abstract":"<div><h3>Background and objective</h3><div>In many jurisdictions, the 14-year threshold is a legally significant factor in determining criminal responsibility and related decisions. We investigated whether third-molar agenesis is associated with differences in the mineralisation stage of the mandibular second molar in South Indian children.</div></div><div><h3>Design</h3><div>Orthopantomograms from 570 children (240 males, 330 females; 10–14.99 years) were staged using Demirjian A to H criteria. Descriptive comparisons were supplemented with a proportional-odds ordinal logistic regression, modelling second-molar stage as the ordered outcome, with agenesis extent, age, and sex as predictors. Results are reported as adjusted odds ratios (aORs).</div></div><div><h3>Results</h3><div>Each additional year of age was associated with substantially higher odds of being in a more advanced second-molar stage (aOR 5.41, 95 % CI 4.47–6.56). Males had lower odds than females of being in a higher stage (aOR 0.58, 95 % CI 0.41–0.81). Relative to children with no third-molar agenesis, the odds of being in a higher second-molar stage were progressively lower with greater agenesis: one missing (aOR 0.53, 95 % CI 0.31–0.91), two missing (aOR 0.39, 95 % CI 0.24–0.62), three missing (aOR 0.26, 95 % CI 0.11–0.62), and all four missing (aOR 0.04, 95 % CI 0.02–0.09).</div></div><div><h3>Conclusion</h3><div>Third-molar agenesis was associated with less advanced mandibular second-molar stages after accounting for age and sex. Agenesis status and extent may be relevant for the 14-year threshold. Future work should develop and externally validate prediction models that integrate third molar agenesis to improve accuracy and minimise misclassification.</div></div>","PeriodicalId":8288,"journal":{"name":"Archives of oral biology","volume":"182 ","pages":"Article 106466"},"PeriodicalIF":2.1,"publicationDate":"2025-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145681571","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 : 2025-12-02DOI: 10.1016/j.archoralbio.2025.106468
Christian Morsczeck, Anja Reck, Michela De Pellegrin, Torsten E. Reichert
Objective
Dental follicle cell lines with a senescence phenotype have a poor differentiation potential into biomineralizing cells. Previous studies have shown that protein kinase C (PKC) and protein kinase B (AKT) regulate the differentiation of DFCs. This study investigates the extent to which regulation of PKC and AKT can improve the differentiation of dental follicle cells with poor osteogenic potential.
Design
Human senescence dental follicle cells with poor osteogenic differentiation potential were osteogenic differentiated with cell culture media containing dexamethasone or bone morphogenetic protein (BMP) 2 as an inducer. GÖ6976 was used as a PKC inhibitor, and MK-2206 as an AKT inhibitor. The AKT activator SC-79 was also used. Western blot analyses were performed with specific antibodies for the active form of AKT, phosphorylated substrate of PKC and collagen 1. Osteogenic differentiation was quantitatively determined by measuring alkaline phosphatase (ALP) activity and biomineralization using alizarin staining. The gene expression of sclerostin (SOST) and PTHLH was quantitatively determined using real-time RT-PCRs.
Results
The results showed that both the inhibitor MK-2206 inhibits AKT and the activator SC-79 can activate AKT in DFCs. Only inhibition of AKT slightly but significantly enhanced osteogenic differentiation. While inhibition of PKC activity apparently only occurred from day 14 of differentiation using the inhibitor GÖ6976, PKC inhibition promoted osteogenic differentiation and inhibits the expression of SOST and Parathyroid hormone-related protein (PTHLH).
Conclusion
Our results suggest that the addition of GÖ6976 is an efficient method to induce biomineralization in senescent DFCs.
{"title":"Inhibition of protein kinase C activity enables mineralization of senescent dental follicle cells with almost no osteogenic differentiation potential","authors":"Christian Morsczeck, Anja Reck, Michela De Pellegrin, Torsten E. Reichert","doi":"10.1016/j.archoralbio.2025.106468","DOIUrl":"10.1016/j.archoralbio.2025.106468","url":null,"abstract":"<div><h3>Objective</h3><div>Dental follicle cell lines with a senescence phenotype have a poor differentiation potential into biomineralizing cells. Previous studies have shown that protein kinase C (PKC) and protein kinase B (AKT) regulate the differentiation of DFCs. This study investigates the extent to which regulation of PKC and AKT can improve the differentiation of dental follicle cells with poor osteogenic potential.</div></div><div><h3>Design</h3><div>Human senescence dental follicle cells with poor osteogenic differentiation potential were osteogenic differentiated with cell culture media containing dexamethasone or bone morphogenetic protein (BMP) 2 as an inducer. GÖ6976 was used as a PKC inhibitor, and MK-2206 as an AKT inhibitor. The AKT activator SC-79 was also used. Western blot analyses were performed with specific antibodies for the active form of AKT, phosphorylated substrate of PKC and collagen 1. Osteogenic differentiation was quantitatively determined by measuring alkaline phosphatase (ALP) activity and biomineralization using alizarin staining. The gene expression of sclerostin (SOST) and PTHLH was quantitatively determined using real-time RT-PCRs.</div></div><div><h3>Results</h3><div>The results showed that both the inhibitor MK-2206 inhibits AKT and the activator SC-79 can activate AKT in DFCs. Only inhibition of AKT slightly but significantly enhanced osteogenic differentiation. While inhibition of PKC activity apparently only occurred from day 14 of differentiation using the inhibitor GÖ6976, PKC inhibition promoted osteogenic differentiation and inhibits the expression of SOST and Parathyroid hormone-related protein (PTHLH).</div></div><div><h3>Conclusion</h3><div>Our results suggest that the addition of GÖ6976 is an efficient method to induce biomineralization in senescent DFCs.</div></div>","PeriodicalId":8288,"journal":{"name":"Archives of oral biology","volume":"182 ","pages":"Article 106468"},"PeriodicalIF":2.1,"publicationDate":"2025-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145681573","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 : 2025-11-28DOI: 10.1016/j.archoralbio.2025.106465
Pengfei Zhao , Xiaohu Lin , Yuanyuan Cao , Zhang Zhao , Xiaoge Zhang , Yang Zhao , Songge Liu , Bo Hu , Wei Cao , Wei Li , Xianjun Zhang
Objectives
To investigate the prognostic significance of Sex-determining region Y-box 4 (SOX4) and epithelial–mesenchymal transition (EMT) markers (E-cadherin, N-cadherin, TWIST1) in oral squamous cell carcinoma (OSCC) and to evaluate their functional role.
Design
A total of 250 OSCC tissues and 80 normal oral mucosa specimens were analyzed by immunohistochemistry for SOX4, E-cadherin, N-cadherin, and TWIST1 expression. Kaplan–Meier survival curves with log-rank tests, Cox proportional hazards regression (univariate and multivariate), and Spearman correlation were performed to assess prognostic value and clinicopathological associations. Functional validation was conducted by SOX4 knockdown and overexpression in OSCC cell lines, followed by migration, invasion, and EMT marker analyses.
Results
High SOX4, N-cadherin, and TWIST1 expression correlated with larger tumor size, lymph node metastasis, advanced clinical stage, and poor differentiation (p < 0.05). SOX4 expression showed positive correlation with N-cadherin and TWIST1, and negative correlation with E-cadherin. Kaplan–Meier analysis demonstrated that high SOX4, N-cadherin, and TWIST1 expression were associated with significantly poorer overall survival. Functional assays confirmed that SOX4 overexpression promoted EMT and cell motility, whereas knockdown reversed these effects.
Conclusions
In summary, our study identified SOX4, N-cadherin, TWIST1, E-cadherin, lymph node metastasis, and clinical staging as independent factors influencing the prognosis of OSCC. SOX4 promotes EMT, thereby influencing the progression and prognosis of OSCC.
{"title":"Evaluation of the correlativity of SOX4 and epithelial-mesenchymal transition markers expression in the prognosis of oral squamous cell carcinoma","authors":"Pengfei Zhao , Xiaohu Lin , Yuanyuan Cao , Zhang Zhao , Xiaoge Zhang , Yang Zhao , Songge Liu , Bo Hu , Wei Cao , Wei Li , Xianjun Zhang","doi":"10.1016/j.archoralbio.2025.106465","DOIUrl":"10.1016/j.archoralbio.2025.106465","url":null,"abstract":"<div><h3>Objectives</h3><div>To investigate the prognostic significance of Sex-determining region Y-box 4 (SOX4) and epithelial–mesenchymal transition (EMT) markers (E-cadherin, N-cadherin, TWIST1) in oral squamous cell carcinoma (OSCC) and to evaluate their functional role.</div></div><div><h3>Design</h3><div>A total of 250 OSCC tissues and 80 normal oral mucosa specimens were analyzed by immunohistochemistry for SOX4, E-cadherin, N-cadherin, and TWIST1 expression. Kaplan–Meier survival curves with log-rank tests, Cox proportional hazards regression (univariate and multivariate), and Spearman correlation were performed to assess prognostic value and clinicopathological associations. Functional validation was conducted by SOX4 knockdown and overexpression in OSCC cell lines, followed by migration, invasion, and EMT marker analyses.</div></div><div><h3>Results</h3><div>High SOX4, N-cadherin, and TWIST1 expression correlated with larger tumor size, lymph node metastasis, advanced clinical stage, and poor differentiation (p < 0.05). SOX4 expression showed positive correlation with N-cadherin and TWIST1, and negative correlation with E-cadherin. Kaplan–Meier analysis demonstrated that high SOX4, N-cadherin, and TWIST1 expression were associated with significantly poorer overall survival. Functional assays confirmed that SOX4 overexpression promoted EMT and cell motility, whereas knockdown reversed these effects.</div></div><div><h3>Conclusions</h3><div>In summary, our study identified SOX4, N-cadherin, TWIST1, E-cadherin, lymph node metastasis, and clinical staging as independent factors influencing the prognosis of OSCC. SOX4 promotes EMT, thereby influencing the progression and prognosis of OSCC.</div></div>","PeriodicalId":8288,"journal":{"name":"Archives of oral biology","volume":"182 ","pages":"Article 106465"},"PeriodicalIF":2.1,"publicationDate":"2025-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145662044","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 : 2025-11-19DOI: 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.
{"title":"Impact of stress on pain sensitization and emotional responses in a rat model of persistent TMJ inflammation","authors":"Jardel Francisco Mazzi-Chaves , Ana Paula Ribeiro Novaes , Glauce Crivelaro Nascimento , Christie Ramos Andrade Leite-Panissi","doi":"10.1016/j.archoralbio.2025.106463","DOIUrl":"10.1016/j.archoralbio.2025.106463","url":null,"abstract":"<div><h3>Objective</h3><div>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.</div></div><div><h3>Design</h3><div>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.</div></div><div><h3>Results</h3><div>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.</div></div><div><h3>Conclusion</h3><div>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.</div></div>","PeriodicalId":8288,"journal":{"name":"Archives of oral biology","volume":"182 ","pages":"Article 106463"},"PeriodicalIF":2.1,"publicationDate":"2025-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145621367","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 : 2025-11-15DOI: 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.
{"title":"Growing new teeth: A systematic review of functional whole-tooth regeneration in orthotopic animal models","authors":"Pei-Jung Wu, Mar Jovani-Sancho","doi":"10.1016/j.archoralbio.2025.106461","DOIUrl":"10.1016/j.archoralbio.2025.106461","url":null,"abstract":"<div><h3>Objective</h3><div>To identify and evaluate current strategies for functional whole-tooth regeneration in orthotopic animal models with high translational potential.</div></div><div><h3>Design</h3><div>A systematic review of <em>in vivo</em> 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.</div></div><div><h3>Results</h3><div>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.</div></div><div><h3>Conclusions</h3><div>PCL-based scaffolding systems may facilitate functional tooth regeneration, but further standardized <em>in vivo</em> research is needed to validate translational potential.</div></div>","PeriodicalId":8288,"journal":{"name":"Archives of oral biology","volume":"182 ","pages":"Article 106461"},"PeriodicalIF":2.1,"publicationDate":"2025-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145566602","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 : 2025-11-15DOI: 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。
{"title":"Tetramethoxyluteolin, an active constituent in mulberry leaves, promotes osteogenesis of jaw bone marrow mesenchymal stem cells in periodontitis microenvironment via NF-κB inhibition","authors":"Yuning Xia , Chao Shan , Zeyu Wu , Jin Zhao","doi":"10.1016/j.archoralbio.2025.106459","DOIUrl":"10.1016/j.archoralbio.2025.106459","url":null,"abstract":"<div><h3>Objective</h3><div>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.</div></div><div><h3>Design</h3><div>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 <em>Porphyromonas gingivalis</em>-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.</div></div><div><h3>Results</h3><div>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.</div></div><div><h3>Conclusion</h3><div>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.</div></div>","PeriodicalId":8288,"journal":{"name":"Archives of oral biology","volume":"182 ","pages":"Article 106459"},"PeriodicalIF":2.1,"publicationDate":"2025-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145566620","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 : 2025-11-15DOI: 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.
{"title":"Is there geometric morphometric evidence for the selection against impaction? A comparative cross-sectional study of specific tooth-agenesis patterns","authors":"Sarah Boussali , Anaïs Cavaré","doi":"10.1016/j.archoralbio.2025.106462","DOIUrl":"10.1016/j.archoralbio.2025.106462","url":null,"abstract":"<div><h3>Objectives</h3><div>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.</div></div><div><h3>Design</h3><div>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.</div></div><div><h3>Results</h3><div>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 (<em>p</em> = 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.</div></div><div><h3>Conclusion</h3><div>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.</div></div>","PeriodicalId":8288,"journal":{"name":"Archives of oral biology","volume":"182 ","pages":"Article 106462"},"PeriodicalIF":2.1,"publicationDate":"2025-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145566631","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}