Archives Of Oral Biology[JOURNAL]
Sun
200 papers
Prognostic and diagnostic evaluation of HSPG2 gene expression in oral squamous cell carcinoma: A case-control study.
Yanyang L, Xiaohua C, Chang C … +3 more , Zhongmao C, Xiaomei H, Xiaoping W
Arch Oral Biol · 2026 Jun · PMID 42398122 · Publisher ↗
OBJECTIVE: This study aimed to evaluate HSPG2 expression in oral squamous cell carcinoma (OSCC) and validate its clinical relevance using external datasets, including The Cancer Genome Atlas (TCGA) and the single-cell GS...
OBJECTIVE: This study aimed to evaluate HSPG2 expression in oral squamous cell carcinoma (OSCC) and validate its clinical relevance using external datasets, including The Cancer Genome Atlas (TCGA) and the single-cell GSE103322 dataset. DESIGN: A matched case-control study (2022-2024) enrolled 25 OSCC patients and 25 age- and sex-matched healthy controls, also balanced for smoking and alcohol status. Biological samples (formalin-fixed paraffin-embedded tissue, blood plasma, and saliva) were collected. RNA was extracted, converted to cDNA, and HSPG2 expression quantified using qRT-PCR. External validation was performed using TCGA, and single-cell analysis utilized GSE103322. Receiver operating characteristic (ROC) curves assessed diagnostic performance. RESULTS: HSPG2 expression was significantly elevated in OSCC tissues (p = 0.002) and blood plasma (p = 0.02), but not in saliva (p = 0.58). Increased expression was observed across genders, all age groups, tumor stages, and grades, and was independent of HPV status. TCGA analysis confirmed higher HSPG2 expression in tumors versus normal tissues across demographic and clinical subgroups, with high expression associated with poorer survival, particularly among African American patients. Single-cell RNA-seq revealed stromal enrichment of HSPG2, predominantly in endothelial cells and fibroblasts. ROC analysis demonstrated good diagnostic performance in tissue (AUC = 0.86) and blood plasma (AUC = 0.84), but limited value in saliva (AUC = 0.57). CONCLUSION: HSPG2 is overexpressed in OSCC tissues and plasma, correlating with tumor stage, grade, and poor survival, especially in African Americans. As a stromal-associated gene promoting tumor progression, HSPG2 holds promise as a diagnostic and prognostic biomarker in OSCC.
Dental traits: From anthropological foundations to clinical implications.
Yang Y, Yang X, Zhang X … +1 more , Hou J
Arch Oral Biol · 2026 Jun · PMID 42391787 · Publisher ↗
OBJECTIVE: Dental traits are a fundamental concept in anthropological studies and hold substantial clinical relevance in dentistry disciplines. This review summarizes research progress on dental traits and discusses thei...
OBJECTIVE: Dental traits are a fundamental concept in anthropological studies and hold substantial clinical relevance in dentistry disciplines. This review summarizes research progress on dental traits and discusses their clinical implications in various fields of dentistry, aiming to provide more scientific foundation for personalized dental diagnosis and treatment. DESIGN: A narrative literature search was conducted across PubMed, Web of Science, Scopus, and Anthropology Plus databases (1914-June 2026), focusing on variations in metric and non-metric dental traits, populational specificity, sexual dimorphism, and their clinical implications in forensic anthropology, orthodontics, prosthodontics, and endodontics. RESULTS: Metric and non-metric dental traits exhibit population-specific and sexual dimorphism, which can not only be used for ancestry and sex determination in anthropology but also provide crucial guidance for orthodontic diagnosis, aesthetic restoration design, predicting complexity in endodontic and periodontal therapies, and enabling personalized dental treatment tailored to population- and sex-specific variations. CONCLUSIONS: Dental traits bridge anthropology and dentistry, but further research is required by greater interdisciplinary collaboration.
Surface properties of irradiated and non-irradiated dentin following pH cycling and fluoride toothpaste exposure: An in vitro study.
de Carvalho AJD, E Silva BVF, Ferreira ALS … +4 more , de Oliveira G, Andrade FG, de Carvalho FG, Novais VR
Arch Oral Biol · 2026 Jun · PMID 42385461 · Publisher ↗
OBJECTIVE: To investigate the effects of irradiation on the surface properties of demineralized human dentin following pH cycling and toothpaste exposure. DESIGN: Twenty sound human third molars were randomly assigned to...
OBJECTIVE: To investigate the effects of irradiation on the surface properties of demineralized human dentin following pH cycling and toothpaste exposure. DESIGN: Twenty sound human third molars were randomly assigned to control and irradiated groups (n = 10 each). Dentin samples were demineralized to induce artificial caries, then subjected to pH cycling and immersion in a toothpaste slurry. Surface changes were assessed using Knoop microhardness (KHN), atomic force microscopy (AFM), and scanning electron microscopy (SEM). RESULTS: At baseline, irradiated dentin showed significantly lower KHN values than control (p = 0.04). After demineralization, both groups exhibited a significant reduction in microhardness (p = 0.04). Following pH cycling and toothpaste exposure, KHN decreased further; however, no significant between-group differences were observed (p > 0.99). Significant intragroup changes occurred across all evaluation periods (p < 0.05). AFM analysis showed no significant intergroup differences in surface roughness; however, roughness increased significantly from baseline to the final evaluation in both groups, with no significant difference between the baseline and demineralized stages. AFM and SEM images demonstrated smooth surfaces at baseline, loss of peritubular material post-demineralization, and increased roughness with mineral deposition after pH cycling, particularly in irradiated dentin. CONCLUSIONS: Under the in vitro conditions evaluated, irradiated and non-irradiated dentin demonstrated comparable microhardness and surface roughness following pH cycling and fluoridated toothpaste exposure. These findings indicate similar surface responses between groups under the experimental conditions tested. Further research is warranted to evaluate the influence of the oral environment, dietary factors, and mechanical abrasion.
CircSSRP1 regulates SMAD3 to affect proliferation and apoptosis of human embryonic palatal mesenchymal cells in nonsyndromic cleft lip with or without cleft palate by sponging miR-708-5p.
Guo S, Guo T, Huang Y … +2 more , Xu Y, Chen R
Arch Oral Biol · 2026 Jun · PMID 42372493 · Publisher ↗
OBJECTIVES: Nonsyndromic cleft lip with or without cleft palate (NSCL/P) is a common oral and maxillofacial congenital anomaly with unknown etiology. This study aimed to investigate the potential regulatory role of the c...
OBJECTIVES: Nonsyndromic cleft lip with or without cleft palate (NSCL/P) is a common oral and maxillofacial congenital anomaly with unknown etiology. This study aimed to investigate the potential regulatory role of the circSSRP1/miR-708-5p/SMAD3 axis in NSCL/P. DESIGN: The circSSRP1/miR-708-5p/SMAD3 axis was predicted via integrated bioinformatics analysis of the GSE42589 and GSE316908 datasets, and its expression was validated in NSCL/P tissues by qRT-PCR. Fluorescence in situ hybridization (FISH) confirmed circSSRP1 subcellular localization. Its effects on proliferation and apoptosis in human embryonic palatal mesenchymal (HEPM) cells were examined in vitro. Dual-luciferase assays, Western blot, and rescue experiments validated molecular interactions. RESULTS: In NSCL/P tissues, circSSRP1 and SMAD3 were upregulated, while miR-708-5p was downregulated. CircSSRP1 was distributed in both cytoplasm and nucleus. Functionally, overexpression of circSSRP1 or knockdown of miR-708-5p inhibited cell proliferation while promoting apoptosis in HEPM cells. Conversely, knockdown of circSSRP1 or overexpression of miR-708-5p produced the opposite effects. Rescue experiments confirmed that miR-708-5p reversed circSSRP1's effects in HEPM cells. Mechanistically, circSSRP1 sponged miR-708-5p to target SMAD3. CONCLUSIONS: We identified a novel circRNA, circSSRP1, which inhibits proliferation while promoting apoptosis in HEPM cells by sponging miR-708-5p and modulating SMAD3 expression. Our study reveals the circSSRP1/miR-708-5p/SMAD3 axis as a critical potential in vitro cytological regulatory network implicated in NSCL/P pathogenesis.
Development of models of preclinical stage 2 bisphosphonate-related osteonecrosis of the jaw in non-rodent mammals using zoledronate: A systematic review.
El Fadhlallah PM, Surboyo MDC, Kesuma A … +5 more , Sato-Yamada Y, Rosenkranz AL, Koga M, Tomihara K, Maekawa T
Arch Oral Biol · 2026 Jun · PMID 42372398 · Publisher ↗
OBJECTIVE: To identify specific experimental parameters, including species selection, zoledronate dosing regimens, and surgical triggers, required to reliably reproduce advanced clinical stages of bisphosphonate-related...
OBJECTIVE: To identify specific experimental parameters, including species selection, zoledronate dosing regimens, and surgical triggers, required to reliably reproduce advanced clinical stages of bisphosphonate-related osteonecrosis of the jaw (BRONJ) in non-rodent mammals. DESIGN: Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, we systematically searched for studies reporting the use of zoledronate-treated non-rodent mammals subjected to dental trauma. Extracted variables included species, dosing, intervention, clinical exposure, histopathology, and micro-CT findings. RESULTS: Twenty-three studies were included. High-dose intravenous zoledronate combined with posterior tooth extraction consistently induced stage 2 BRONJ across various species, including minipigs, dogs, and sheep. Key findings included persistent bone exposure, increased empty osteocytic lacunae, and necrotic bone areas. CONCLUSIONS: Standardized protocols using large animal models effectively mimic human stage 2 BRONJ, providing a reliable platform for translational research and the development of new therapeutic strategies.
Impact of lifestyle factors on salivary nitrite and nitrate concentrations in overweight/obese individuals.
Guo K, Joshipura K, Ricart K … +2 more , Patel RP, Morou-Bermudez E
Arch Oral Biol · 2026 Jun · PMID 42372397 · Publisher ↗
OBJECTIVE: This study aimed to evaluate the association of lifestyle factors (smoking, physical activity, consumption of sugar-sweetened beverages and alcohol, and oral hygiene practices) with salivary nitrite and nitrat...
OBJECTIVE: This study aimed to evaluate the association of lifestyle factors (smoking, physical activity, consumption of sugar-sweetened beverages and alcohol, and oral hygiene practices) with salivary nitrite and nitrate concentrations. DESIGN: This cross-sectional study included 1076 overweight/obese adults (aged 40-65 years) from the San Juan Overweight Adult Longitudinal Study (SOALS). Salivary nitrite and nitrate concentrations were measured using Eicom's ENO-30. Associations between lifestyle factors and salivary nitrite/nitrate concentrations were evaluated using Wilcoxon rank-sum test, Kruskal-Wallis with Dunn's test, Spearman correlation, and Gamma regression controlling for age, sex, metabolic syndrome, and bleeding on probing. RESULTS: Smoking (former and current), sugar-sweetened beverage consumption, and plaque index were associated with lower salivary nitrite or nitrate concentrations (p < 0.001-0.048). Twice-daily brushing (p = 0.025) and daily flossing (p = 0.015) were associated with higher salivary nitrite compared to less frequent practices. Over-the-counter mouthwash use (≥2 times daily) was positively associated with nitrate concentrations (p = 0.028). No significant associations were observed for alcohol consumption and physical activity. CONCLUSIONS: Optimal oral hygiene practices are positively associated with salivary nitrate and nitrite concentrations, while smoking and sugar-sweetened beverages consumption show negative associations. This highlights their potential relevance for oral and cardiometabolic health in individuals with overweight or obese.
Effects of hypoxia and compressive stress on the expression of angiogenic factors in dental pulp cells.
Shen S, Yang W, Tu J … +4 more , Huang Q, Huang C, An X, Si Q
Arch Oral Biol · 2026 Jun · PMID 42372396 · Publisher ↗
OBJECTIVES: Regenerative endodontic therapy offers a highly promising solution for functional dental pulp regeneration; however, reconstructing a functional vascular network remains the core bottleneck. This study invest...
OBJECTIVES: Regenerative endodontic therapy offers a highly promising solution for functional dental pulp regeneration; however, reconstructing a functional vascular network remains the core bottleneck. This study investigated the synergistic effects of hypoxia and compressive stress on dental pulp cells angiogenic activity. DESIGN: This study established an in vitro model that combines hypoxic conditions and compressive loading conditions to simulate the complex microenvironment for DPCs. Cellular proliferation was quantified via Cell Counting Kit-8 assays, migration ability was assessed by scratch wound assays, and angiogenesis-related gene/protein expression was analyzed using real-time quantitative polymerase chain reaction and Western blotting. Functional vascularization potential was assessed through tube formation assays. RESULTS: Both hypoxia and compressive stress significantly induced angiogenic cytokine expression in DPCs. Sustained co-stimulation, however, attenuated hypoxia's regulatory efficacy. Temporal profiling revealed peak angiogenic factor expression occurred markedly earlier under mechanical loading (2 h post-stimulation) versus hypoxia alone (16-24 h). CONCLUSIONS: Both hypoxic conditions and short-duration compressive stress upregulated pro-angiogenic factor expression in DPCs. However, compressive stress exerted a more rapid regulatory effect, while hypoxia induced slower-developing but more sustained upregulation.
Occlusal abnormalities and temporomandibular joint osteoarthritis: A narrative review of cross-scale mechanical-metabolic-immune mechanisms.
Huang X, Tao Y, Huang Z … +2 more , Zhao Z, Cen X
Arch Oral Biol · 2026 Jun · PMID 42364313 · Publisher ↗
OBJECTIVE: To synthesize recent multiscale evidence and propose a unified mechanical-metabolic-immune framework for the role of occlusal abnormalities in temporomandibular joint osteoarthritis (TMJOA) pathogenesis. DESIG...
OBJECTIVE: To synthesize recent multiscale evidence and propose a unified mechanical-metabolic-immune framework for the role of occlusal abnormalities in temporomandibular joint osteoarthritis (TMJOA) pathogenesis. DESIGN: A narrative literature search was conducted in PubMed/MEDLINE, Scopus, and Web of Science for English-language articles published between January 2011 and April 2026. Search terms combined concepts related to temporomandibular joint osteoarthritis, malocclusion or occlusal abnormalities, mechanotransduction, Piezo1, integrin signaling, mitochondrial dysfunction, cGAS-STING activation, single-cell transcriptomics, macrophages, and sexual dimorphism. Clinical, imaging, animal, cellular, omics-based, and mechanistic studies relevant to TMJOA were narratively synthesized. RESULTS: Occlusal abnormalities may alter mandibular kinematics and joint stress distribution, thereby activating mechanotransduction through Piezo1, integrins, and related developmental feedback loops. Sustained mechanical overload may promote calcium dysregulation, endoplasmic reticulum stress, mitochondrial dysfunction, and activation of the cGAS-STING pathway. These changes can shift cellular metabolism toward increased glycolysis and contribute to a pro-inflammatory microenvironment. Single-cell and lineage-tracing evidence further suggests that sex-related immune regulation, including macrophage ontogeny and Xist-associated inflammatory responses, may contribute to the female predominance of temporomandibular joint disorders, although TMJ-specific validation remains needed. CONCLUSIONS: TMJOA progression can be interpreted as a cross-scale process in which abnormal occlusal loading links biomechanical stress, metabolic dysfunction, and immune remodeling. These pathways may represent potential targets for future mechanism-based diagnosis and therapy.
Cyanobacterial fatty acid esters disrupt polymicrobial oral biofilms and exhibit potential interactions with adhesion proteins and virulence-associated targets.
Bharathidasan P, Ganapathy D, Balasubramaniyan P … +1 more , Antonyraj APM
Arch Oral Biol · 2026 Jun · PMID 42349046 · Publisher ↗
OBJECTIVE: Oral biofilm-associated infections are difficult to manage because of their polymicrobial nature, antimicrobial tolerance, and involvement in chronic oral diseases. This study evaluated the antimicrobial, anti...
OBJECTIVE: Oral biofilm-associated infections are difficult to manage because of their polymicrobial nature, antimicrobial tolerance, and involvement in chronic oral diseases. This study evaluated the antimicrobial, anti-biofilm, and antioxidant potential of bioactive metabolites from the freshwater cyanobacterium Oscillatoria sp. PB602 against oral biofilm-associated pathogens and clinically relevant opportunistic colonizers implicated in complex oral infections. DESIGN: Methanolic extracts of Oscillatoria sp. PB602 were evaluated against oral pathogens and opportunistic colonizers, including Streptococcus mutans, Staphylococcus aureus, Escherichia coli, Enterococcus faecalis, Pseudomonas aeruginosa, and Candida albicans, using agar diffusion and Minimum Inhibitory Concentration (MIC) assay. Anti-biofilm activity was assessed by crystal violet staining and Confocal Laser Scanning Microscopy (CLSM), while bioactive metabolites were characterized using Gas Chromatography-Mass Spectrometry (GC-MS) and Fourier Transform Infrared Spectroscopy (FT-IR). Molecular docking analysis was performed to investigate potential interactions with biofilm-associated virulence proteins. RESULTS: The extract demonstrated concentration-dependent antimicrobial activity, with the highest inhibition observed against C. albicans (16 mm at 100 μg/mL). MIC analysis showed > 88% inhibition of mixed-species biofilms. Crystal violet assays revealed an 84% reduction in biofilm biomass, while CLSM confirmed ∼87% microbial cell death in mature biofilms at 2.5 × MIC. GC-MS identified fatty acid esters, including oleic acid derivatives, and FT-IR confirmed hydroxyl, carbonyl, and amine functional groups. Docking analysis indicated moderate binding affinity toward virulence-related proteins, with binding energies up to -5.8 kcal/mol. CONCLUSION: Oscillatoria sp. PB602 exhibited antimicrobial, anti-biofilm, and antioxidant activities against oral biofilm-associated pathogens and opportunistic colonizers, supporting its potential as a natural source of bioactive metabolites for oral healthcare applications and contributing to Sustainable Development Goal (SDG) 3 (Good Health and Well-being) through the advancement of preventive oral healthcare strategies.
Effects of Er:YAG laser irradiation on rough titanium surface properties and osteoblast-like cell responses in the absence or presence of carbonate apatite.
Hojo T, Kajiya H, Goto K … +3 more , Seki T, Ayukawa Y, Tsuzuki T
Arch Oral Biol · 2026 Jun · PMID 42341388 · Publisher ↗
OBJECTIVES: This study investigated the effects of erbium-doped yttrium aluminum garnet (Er:YAG) laser irradiation on rough titanium surface properties and osteoblast-like cell responses in the absence or presence of car...
OBJECTIVES: This study investigated the effects of erbium-doped yttrium aluminum garnet (Er:YAG) laser irradiation on rough titanium surface properties and osteoblast-like cell responses in the absence or presence of carbonate apatite (CO₃Ap) as a bone substitute. DESIGN: Rough titanium plates were prepared as nonirradiated or irradiated by an Er:YAG laser using clinically applicable parameters. The surface morphology was examined through scanning electron microscopy (SEM), and the wettability and surface roughness (Ra) were measured. MC3T3-E1 cells were cultured on titanium plates in the absence or presence of COAp. Cell viability was assessed on days 1 and 5 after cell seeding, and alkaline phosphatase (ALP) activity was assessed on days 1 and 7. Calcium ion (Ca²⁺) concentrations were measured in three cell-free solutions. RESULTS: Er:YAG irradiation produced no apparent SEM-detectable surface morphological changes while improving surface wettability and increasing Ra. Cell viability was generally higher in the presence of CO₃Ap, and the highest value was observed on irradiated titanium in the presence of CO₃Ap on day 5. ALP activity was higher in the presence of CO₃Ap on day 7 and was also increased by Er:YAG irradiation in the absence of COAp. CO₃Ap modulated Ca²⁺ concentration in a solution-dependent manner. CONCLUSIONS: Er:YAG irradiation improved the wettability and increased the surface roughness without any SEM-detectable morphological changes. In the presence of CO₃Ap as a bone substitute, Er:YAG-irradiated titanium surfaces may be compatible with osteoblast-like cell responses in vitro. Further studies are required to clarify the clinical relevance of this approach.
Regulatory roles of gingival fibroblasts in periodontal homeostasis and inflammatory progression.
Liu S, Zhao Z, Liu N … +1 more , Liu Q
Arch Oral Biol · 2026 Jun · PMID 42335856 · Publisher ↗
OBJECTIVES: To synthesise current evidence on the heterogeneity and functional roles of gingival fibroblasts in periodontal homeostasis and periodontitis progression. DESIGN: A narrative review was conducted using struct...
OBJECTIVES: To synthesise current evidence on the heterogeneity and functional roles of gingival fibroblasts in periodontal homeostasis and periodontitis progression. DESIGN: A narrative review was conducted using structured searches of PubMed, Web of Science and CNKI from inception to November 2025, with predefined keywords related to gingival fibroblasts, periodontitis, and periodontal homeostasis. RESULTS: Evidence indicates that gingival fibroblasts exhibit substantial functional plasticity and subpopulation heterogeneity, as revealed by single-cell and spatial transcriptomic analyses. Under physiological conditions, homeostatic gingival fibroblasts maintain extracellular matrix integrity, support alveolar bone homeostasis, and contribute to immune surveillance. In contrast, during periodontitis, gingival fibroblasts undergo phenotypic transitions toward pro-inflammatory states, characterised by increased secretion of cytokines, upregulation of matrix metalloproteinases, and promotion of osteoclastogenesis. These alterations enhance extracellular matrix degradation and alveolar bone resorption, thereby accelerating disease progression. Emerging evidence further highlights their central role in coordinating immune responses and tissue remodelling within the periodontal microenvironment. CONCLUSIONS: Gingival fibroblasts are vital orchestrators of periodontal homeostasis and disease. Their phenotypic switching underlies the transition from tissue maintenance to destruction. Targeting fibroblast heterogeneity and function offers a promising avenue for precision diagnostics and regenerative therapies in periodontitis.
Periodontal pathogen-driven endotoxemia and bacteremia as a mechanistic link to liver disease. A scoping review.
da Silva Barbirato D, Fogacci MF, Guimarães TC … +4 more , Carneiro JRI, de Barros MCM, Shibli JA, de Molon RS
Arch Oral Biol · 2026 Jun · PMID 42330718 · Publisher ↗
OBJECTIVE: This scoping review aimed to map and synthesize the available evidence linking periodontal pathogen-derived endotoxemia and bacteremia to liver abnormalities and to identify the biological mechanisms potential...
OBJECTIVE: This scoping review aimed to map and synthesize the available evidence linking periodontal pathogen-derived endotoxemia and bacteremia to liver abnormalities and to identify the biological mechanisms potentially involved in hepatic injury. DESIGN: Following PRISMA-ScR guidelines, comprehensive electronic searches were conducted across major databases, including MEDLINE, Embase, Scopus, Web of Science, and Cochrane CENTRAL, complemented by grey literature sources. Experimental and clinical studies reporting endotoxemia and/or bacteremia attributable to periodontal pathogens in association with liver-related outcomes were included without restrictions on study design or language. Data extraction and study selection were performed in duplicate. Methodological appraisal was conducted using the SYRCLE risk of bias tool for animal studies and the Joanna Briggs Institute checklist for case reports. RESULTS: Twenty studies met the inclusion criteria, comprising experimental animal studies and clinical case reports. Porphyromonas gingivalis was the most frequently investigated pathogen, followed by Aggregatibacter actinomycetemcomitans and Fusobacterium nucleatum. Experimental evidence consistently demonstrated that periodontal pathogen-derived endotoxemia and bacteremia promote hepatic inflammation, oxidative stress, lipid dysregulation, steatosis, hepatocyte injury, and fibrogenic remodeling. Reported mechanisms included activation of Toll-like receptor signaling, Galectin-3 accumulation, TGF-β1/Smad-mediated fibrogenesis, hepatic stellate cell activation, and endoplasmic reticulum stress. Clinical reports further linked odontogenic infections to severe hepatic complications, including pyogenic liver abscesses and cirrhosis. CONCLUSION: The available evidence supports a biologically plausible role for periodontal pathogen-derived endotoxemia and bacteremia in the initiation and progression of liver disease. However, the current evidence base is predominantly preclinical, highlighting the need for well-designed human studies to establish causality and clinical relevance.
Ossification of the mandible: A regional composite model of intramembranous, parachondral, and endochondral mechanisms.
Rusu MC, Stănescu AG, Tudose RC
Arch Oral Biol · 2026 Jun · PMID 42320182 · Publisher ↗
OBJECTIVE: To catalogue the ossification mechanisms operating along the proximal-distal axis of the human mandible and integrate them into a unified regional framework. DESIGN: Narrative review of embryological, molecula...
OBJECTIVE: To catalogue the ossification mechanisms operating along the proximal-distal axis of the human mandible and integrate them into a unified regional framework. DESIGN: Narrative review of embryological, molecular, transcriptomic, and clinical genetics evidence identified through structured searches of PubMed, Scopus, and Web of Science. The type of evidence (human, animal, in vitro, or combined) underpinning each major finding was tracked. RESULTS: Five non-overlapping mechanisms operate across ten mandibular regions: (i) intramembranous ossification of the body, ramus, and coronoid process; (ii) parachondral ossification, defined as intramembranous bone formation in mesenchyme adjacent to Meckel's cartilage (MC) under MC-derived paracrine guidance (BMP5, BMP7, FGF7, SEMA3A from the intermediate MC) and used as the operative descriptor for mandibular body formation; (iii) endochondral ossification of primary cartilage at the symphysis and anterior MC midsegment, via chondrocyte-to-osteoblast transdifferentiation; (iv) endochondral ossification of secondary cartilage at the condylar and angular processes, with viable hypertrophic chondrocytes and chondroid bone; and (v) perichondral ossification at the MC surface. Transdifferentiation executes mechanism (iii) and is not a separate mode. Posterior MC degradation proceeds via autophagy, apoptosis, and chondroclastic resorption, with independent chondral centres near dental primordia contributing further. Treacher Collins syndrome, cleidocranial dysplasia, and Pierre Robin sequence reflect disruptions at different mechanistic levels. CONCLUSIONS: The mandible is a composite structure employing multiple ossification modes in a region-specific manner; parachondral ossification most accurately characterises mandibular body formation. The framework carries translational implications for tissue engineering, distraction osteogenesis, and prenatal molecular rescue, evidenced only preclinically in a Treacher Collins mouse model.
Third molar agenesis: An updated systematic review and meta-analysis.
Angelakopoulos N, Merdietio Boedi R, Franco A … +3 more , Gkantidis N, De Luca S, Pandis N
Arch Oral Biol · 2026 Jun · PMID 42320181 · Publisher ↗
OBJECTIVE: Third molars (M3s) are the teeth most frequently affected by agenesis in modern human permanent dentition. Despite extensive research, reported prevalence rates vary considerably across populations and study d...
OBJECTIVE: Third molars (M3s) are the teeth most frequently affected by agenesis in modern human permanent dentition. Despite extensive research, reported prevalence rates vary considerably across populations and study designs. The present systematic review and meta-analysis aimed to provide an updated global estimate of the prevalence and patterns of M3 agenesis by incorporating evidence published since the previous comprehensive review by Carter and Worthington (2016). DESIGN: A systematic search was performed in PubMed, Scopus, Virtual Health Library, SciElo, and Open Access Theses and Dissertations to identify relevant studies reporting radiographically diagnosed M3 agenesis in individuals aged ≥ 11 years. Random-effects meta-analyses were performed to estimate pooled prevalence and to examine differences according to sex and jaw. RESULTS: A total of 125 data points comprising 87,282 individuals were included. The pooled global prevalence of M3 agenesis was 23.07% (95% CI: 21.2-25.0%), with substantial heterogeneity across studies (I² =97.6%). No significant difference was observed between prevalence estimates from the earlier dataset and newly included studies (2015-2025). Sex stratified analysis indicated slightly lower odds of agenesis in males compared to females (OR = 0.84, 95% CI: 0.71-0.99). Jaw-specific analysis revealed higher odds of agenesis in the maxilla than in the mandible (OR = 1.56, 95% CI: 1.12-2.18). CONCLUSION: These outcomes confirm that agenesis of at least one M3 affects approximately one quarter of the global population - a finding that can be relevant and should be considered by professionals in clinical, forensic, and academic contexts.
Vertical facial discrepancies in Brazilian children and adolescents are associated with polymorphisms in members of the Wnt gene family.
Reis GHM, Silva AT, Cruz IS … +9 more , Pedreira FRO, Cruvinel BJDM, Gollino S, Stuani MBS, Küchler EC, Kirschneck C, Almeida-Júnior LA, de Oliveira DSB, Reis CLB
Arch Oral Biol · 2026 Jun · PMID 42314243 · Publisher ↗
OBJECTIVES: Vertical facial discrepancies (VFD) are common craniofacial conditions influenced by genetic and environmental factors. This study investigated whether single-nucleotide polymorphisms (SNPs) in the WNT10A and...
OBJECTIVES: Vertical facial discrepancies (VFD) are common craniofacial conditions influenced by genetic and environmental factors. This study investigated whether single-nucleotide polymorphisms (SNPs) in the WNT10A and WNT11 genes are associated with VFD in Brazilian children and adolescents. DESIGN: This study included 247 orthodontic patients aged 5-16 years. VFD was assessed using the VERT index from lateral cephalograms. Six SNPs in WNT10A (rs3806557, rs10177996) and WNT11 (rs596339, rs689095, rs1533767, rs1568507) were genotyped using real-time PCR. Cephalometric measures were summarized by principal component analysis (PCA). Associations were tested using univariate analyses and multivariate Robust Poisson regression models, adjusted for relevant covariates, with uncorrected p-values (alpha = 5%). Prevalence Ratios (PRs) and 95% Confidence Intervals (CIs) were calculated. RESULTS: The rs689095 (p = 0.037; PR = 1.97; CI 95% 1.05-3.71) and rs1568507 (p = 0.049; PR = 1.96; CI 95% 1.00-3.83) SNPs in WNT11 were associated with a light dolichofacial pattern in both univariate and multivariate analyses (p < 0.05). The rs3806557 (WNT10A) genotype was associated with a higher prevalence of dolicho- and severe dolichofacial patterns (p = 0.047; PR = 2.11; 95% CI 1.01-4.42) and with higher mandibular rotation (p = 0.002; β = 0.76; Standard Error = 0.24). The rs10177996 (WNT10A) was also associated with higher mandibular rotation (p = 0.015; β = 0.51; Standard Error=0.21). CONCLUSION: SNPs in WNT10A and WNT11 are associated with VFD in Brazilian children and adolescents. These results suggest that the Wnt signaling pathway may contribute to craniofacial development and highlight potential genetic markers for predicting VFD.
Facilitatory effects of LY404187, a positive allosteric modulator of AMPA receptors, on swallowing initiation in anesthetized male rats.
Yoshihara M, Tsujimura T, Suzuki T … +7 more , Hamashima H, Ono M, Pan CR, Norimine Y, Shirato M, Magara J, Inoue M
Arch Oral Biol · 2026 Jun · PMID 42314242 · Publisher ↗
OBJECTIVE: The present study aimed to investigate the effects of the systemic administration of LY404187, a positive allosteric modulator of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPAR), on swal...
OBJECTIVE: The present study aimed to investigate the effects of the systemic administration of LY404187, a positive allosteric modulator of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPAR), on swallowing function. DESIGN: Experiments were conducted on 78 male Sprague-Dawley rats anesthetized with urethane. Upper airway distention with continuous airflow and the topical laryngeal application of distilled water or capsaicin were used to induce swallowing, which was identified by electromyographic activity recordings from the mylohyoid and thyrohyoid muscles. We investigated the effects of systemic administration of LY404187 (0.25-5.0 mg/kg), an angiotensin-converting enzyme inhibitor (perindopril), a dopamine agonist (amantadine), or a benzodiazepine inverse agonist (S-8510) on swallowing initiation. RESULTS: An optimal concentration of LY404187 (1.0 mg/kg) significantly increased the number of airflow-induced swallows compared with before administration. However, LY404187 did not modulate the initiation of chemically induced swallows. The pre-administration of talampanel, an AMPAR antagonist, diminished facilitatory effects of LY404187 on airflow-induced swallows. Perindopril, amantadine, and S-8510 did not facilitate both mechanically and chemically induced swallows. CONCLUSION: These results suggest that LY404187 facilitates the initiation of mechanically induced swallows via AMPAR activation.
Hypoxia-induced inflammation and protective autophagy in dental pulpitis.
Wang X, Zhang Y, Wu Z … +3 more , Ma L, Lian B, Zhao J
Arch Oral Biol · 2026 Jun · PMID 42314241 · Publisher ↗
OBJECTIVE: Autophagy is critical for cellular homeostasis and may participate in the pathogenesis of pulpitis, although its underlying mechanisms remain unclear. This study investigated hypoxia-induced autophagy in human...
OBJECTIVE: Autophagy is critical for cellular homeostasis and may participate in the pathogenesis of pulpitis, although its underlying mechanisms remain unclear. This study investigated hypoxia-induced autophagy in human dental pulp cells (HDPCs) and its molecular basis. DESIGN: HDPCs were exposed to hypoxic conditions (1% O₂). Cell proliferation, apoptosis, inflammatory cytokine levels, and autophagy markers and autophagic flux were evaluated with or without 3-methyladenine (3-MA) treatment. RNA sequencing was performed to compare healthy and inflamed human dental pulp tissues. RESULTS: Hypoxia significantly inhibited HDPCs proliferation, promoted cell apoptosis, and enhanced the secretion of tumor necrosis factor-alpha, interleukin-6, and interleukin-1β. Meanwhile, hypoxia activated autophagic flux, as evidenced by increased autophagosome formation, elevated microtubule-associated protein 1 light chain 3 beta II (LC3B-II) levels, and reduced sequestosome-1 (SQSTM1/p62) expression; these effects were reversible by 3-MA treatment. Autophagy inhibition exacerbated hypoxic damage to HDPCs, confirming its protective role. RNA- sequencing revealed enrichment of autophagy-related pathways (Mitophagy-animal; Autophagy-animal) in inflamed pulp and identified two core upregulated genes: BCL2 interacting protein 3 pseudogene 11 (BNIP3P11) and cathepsin B (CTSB) were identified. CONCLUSIONS: Hypoxia elicits cytoprotective autophagy in HDPCs under pulpitis-associated stress. The BNIP3P11-CTSB axis may regulate autophagic flux and cellular homeostasis, representing a potential therapeutic target for pulpitis.
A historical perspective on the discovery of human dental follicle cells for regenerative dentistry.
Morsczeck C, Reck A, Reichert TE
Arch Oral Biol · 2026 Jun · PMID 42308583 · Publisher ↗
OBJECTIVES: This narrative review aims to summarize and contextualize more than two decades of research on human dental follicle cells (DFCs), focusing on their biological characteristics, regenerative capacity, and pote...
OBJECTIVES: This narrative review aims to summarize and contextualize more than two decades of research on human dental follicle cells (DFCs), focusing on their biological characteristics, regenerative capacity, and potential applications in dentistry and immunotherapy. DESIGN: Articles were selected based on the literature of non-human propedeutics since the 1990s and human DFC research since its inception in 2005. The focus was set on the isolation, characterization, cultivation, and therapeutic prospects of DFCs as progenitor cells derived from the mesodermal tooth germ. RESULTS: DFCs exhibit multipotent differentiation potential and pronounced immunomodulatory properties. Their developmental origin not only provides specific insights into the cellular processes underlying tooth formation and the regeneration of dental tissue, but also opens up perspectives for novel therapies in dentistry, such as the formation of a biological tooth root. CONCLUSIONS: The findings highlight the potential of DFCs for regenerative dentistry and immunotherapies in general, and provide a solid basis for future work in these research areas.
Local vitamin D bioactivation in oral tissue, from inactive to influential: A narrative review.
Andrukhov O, Hilberath S, Holzmann M … +2 more , Laky M, Behm C
Arch Oral Biol · 2026 Jun · PMID 42275922 · Publisher ↗
OBJECTIVES: Vitamin D status profoundly affects oral health and disease. Over the last decade, evidence has emerged that vitamin D activation can also occur in peripheral tissues. This narrative review was conducted to c...
OBJECTIVES: Vitamin D status profoundly affects oral health and disease. Over the last decade, evidence has emerged that vitamin D activation can also occur in peripheral tissues. This narrative review was conducted to critically analyze the state of the art about the presence and activity of enzymes involved in the bioactivation of vitamin D in the oral tissues. DESIGN: A comprehensive literature search was performed in PubMed and Google Scholar. The search included articles published in English without any time limit. Keywords included but not limited to the combinations of: "vitamin D", "25(OH)D", "1,25(OH)D", "oral tissues", "megalin", "CYP27B1", "extrarenal", and "antimicrobial peptides". Further studies were identified by screening the reference lists of the relevant publications. RESULTS: Various vitamin D metabolites influence the inflammatory response and the production of antimicrobial peptides in various oral cells. The enzyme CYP27B1, which is responsible for the conversion of 25(OH)D into 1,25(OH)D and its bioactivation, is present in various oral tissues and cells. The existence and physiological significance of local vitamin D activation in oral tissues remain unclear. Most of 25(OH)D is bound to the vitamin D-binding protein (DBP) and must be dissociated for activation. It is unclear whether and how this uncoupling occurs in oral tissue. CONCLUSION: Currently, there is rather indirect evidence that vitamin D could be bioactivated in oral tissues. Further studies on the local conversion of vitamin D to 25(OH)D and, subsequently, to 1,25(OH)D in oral tissue, their regulation, and the role of free and bioavailable vitamin D metabolites are required.
Remodelling of intrinsic tongue muscles in a Duchenne muscular dystrophy mouse model: regional differences in fibre size and regeneration.
Koshi E, Ait-Lounis A, Neff LA … +3 more , Dorchies OM, Kiliaridis S, Antonarakis GS
Arch Oral Biol · 2026 Jun · PMID 42269308 · Publisher ↗
OBJECTIVES: To assess muscle fibre size, fibre damage, regeneration, and fibrosis in intrinsic longitudinal tongue muscles in a mouse model of Duchenne muscular dystrophy (DMD). DESIGN: A cross-sectional study was conduc...
OBJECTIVES: To assess muscle fibre size, fibre damage, regeneration, and fibrosis in intrinsic longitudinal tongue muscles in a mouse model of Duchenne muscular dystrophy (DMD). DESIGN: A cross-sectional study was conducted using mdx dystrophic and wild-type (WT) mice at 3, 6, and 12 months of age (5-7 animals per genotype per time point). Tongue and masseter samples were cryosectioned (10 µm) and stained for analysis. Standardised regions of interest were placed in the superior longitudinal (SL) and inferior longitudinal (IL) tongue muscles. Fibre size was assessed using fibre number and minimum Feret diameter; regeneration by centrally nucleated fibres; fibrosis by Sirius Red staining; and fibre damage by immunoglobulin M (IgM) uptake. The masseter muscle was evaluated as a comparative reference. Differences by genotype (mdx vs WT) and muscle region (SL vs IL) were analysed using two-way repeated measures ANOVA; data were pooled across ages, as no significant age effects were found. RESULTS: Genotype and muscle region significantly influenced remodelling in intrinsic tongue muscles. In dystrophic mice, fibres were larger in the IL than the SL muscle (p = 0.002), whereas no regional difference was observed in WT mice. Regeneration was increased in dystrophic tongues and was higher in the IL than the SL muscle (p < 0.001). Collagen deposition differed by muscle region but showed no effects of genotype, and IgM-positive fibres were rare. CONCLUSIONS: Intrinsic tongue muscles in mice with DMD exhibit structural alterations characterized by compensatory fibre hypertrophy and modest regeneration, with pronounced regional differences between longitudinal muscles.
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