Archives of oral biology最新文献

{"title":"Targeting oral cancer with MicroRNA-based therapeutics: The role of tumor-suppressor miRNAs and exosome delivery","authors":"Trupti Janivarad ,&nbsp;Vijay M. Kumbar ,&nbsp;Raghavi Marakatti ,&nbsp;Sanjana Kotabagi ,&nbsp;Manjula Kambi ,&nbsp;Krutika Lolsure ,&nbsp;Ramesh Paranjape","doi":"10.1016/j.archoralbio.2026.106562","DOIUrl":"10.1016/j.archoralbio.2026.106562","url":null,"abstract":"<div><h3>Objective</h3><div>To evaluate the potential of tumor-suppressor microRNAs delivered via exosomes, especially those from human dental pulp stem cells, as a targeted therapy for oral cancer and to examine recent strategies that improve their delivery and clinical application. Although extensive preclinical evidence supports the anticancer functions of TS-miRNAs, the robustness and reproducibility of their effects vary substantially across experimental models. Exosome-based delivery has emerged as a biologically attractive strategy to improve miRNA stability, targeting specificity, and therapeutic efficacy.</div></div><div><h3>Design</h3><div>This review examines preclinical and translational studies on the delivery of tumor-suppressor microRNAs using exosomes, focusing on human dental pulp stem cell derived exosomes and recent strategies that enhance their targeting and therapeutic effectiveness. Relevant studies were identified through PubMed, Scopus, Web of Science, and Google Scholar.</div></div><div><h3>Results</h3><div>Studies show that using exosomes to deliver tumor-suppressor microRNAs can make them more stable, help them enter cells more efficiently, and reach tumors more effectively. Among multiple clinically relevant sources, including bone marrow and adipose-derived mesenchymal stem cells (MSCs), induced pluripotent stem cells (iPSCs), and tumor-derived vesicles, human dental pulp stem cell (hDPSC)-derived exosomes represent a promising, though not yet <em>potential advantages suggested by preclinical studies.</em> Exosomes from human dental pulp stem cells are especially promising, as they are highly compatible with the body and naturally target cancer cells better than other above sources. Engineering these exosomes can further improve their precision and reduce unwanted effects. However, challenges like producing them on a large scale, maintaining consistency, and applying them in real-world clinical settings still remain.</div></div><div><h3>Conclusion</h3><div>Exosome-mediated delivery of tumor-suppressor miRNAs offers an exciting and promising direction in oral cancer therapy. By combining the regulatory power of miRNAs with the natural delivery capacity of exosomes, this strategy could open new possibilities for safer, more effective, and personalized treatment of oral cancer. This review critically evaluates mechanistic evidence, compares exosome sources, and outlines realistic translational barriers, avoiding overstatement of near-term clinical applicability.</div></div>","PeriodicalId":8288,"journal":{"name":"Archives of oral biology","volume":"186 ","pages":"Article 106562"},"PeriodicalIF":2.1,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147387861","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}

{"title":"Amelogenin promotes cellular activation of stem cells derived from human exfoliated deciduous teeth through CD63-mediated ERK1/2 phosphorylation","authors":"Akira Hirabae,&nbsp;Ryo Kunimatsu,&nbsp;Yuki Yoshimi,&nbsp;Kodai Rikitake,&nbsp;Shintaro Ogashira,&nbsp;Rio Shibata,&nbsp;Naonomu Okimura,&nbsp;Io Koyanagi,&nbsp;Ayano Kubota,&nbsp;Tomohiro Ogasawara,&nbsp;Ayaka Nakatani,&nbsp;Kotaro Tanimoto","doi":"10.1016/j.archoralbio.2026.106564","DOIUrl":"10.1016/j.archoralbio.2026.106564","url":null,"abstract":"<div><h3>Objectives</h3><div>Stem cells from human exfoliated deciduous teeth (SHED) represent a minimally invasive source of mesenchymal stem cells for dental tissue regeneration. Although amelogenin, a major enamel matrix protein, is known to enhance the regenerative potential of various dental-derived stem cells, the mechanism—particularly the involvement of the CD63 receptor and extracellular signal-regulated kinase (ERK)1/2 signaling pathway— through which it activates SHED remains unclear. This study aimed to evaluate the effects of amelogenin on cell proliferation and migration in SHED and elucidate the mechanism of signaling via the CD63 receptor.</div></div><div><h3>Design</h3><div>Primary SHED were isolated from exfoliated deciduous teeth and cultured. Cellular activation by amelogenin (1000 ng/mL) was assessed via migration (scratch assay), proliferation (live-cell imaging and 5-bromo-2′-deoxyuridine incorporation), immunofluorescence for CD63 expression, western blotting, and enzyme-linked immunosorbent assay for ERK1/2 phosphorylation. The functional roles of CD63 and ERK1/2 were analyzed using an anti-CD63 neutralizing antibody and MEK1/2 inhibitor U0126.</div></div><div><h3>Results</h3><div>Amelogenin significantly enhanced both the migration and proliferation of SHED compared to the controls. Immunostaining demonstrated that amelogenin increased CD63 expression in SHED. Amelogenin also elevated ERK1/2 phosphorylation, and blockade of CD63 or MEK1/2 abrogated amelogenin-induced increases in cell proliferation, DNA synthesis, and ERK1/2 phosphorylation.</div></div><div><h3>Conclusions</h3><div>Amelogenin promotes the migration and proliferation of SHED through CD63-mediated ERK1/2 signaling, highlighting a promising approach for enhancing cell-based repair of refractory bone defects in dental regenerative medicine.</div></div>","PeriodicalId":8288,"journal":{"name":"Archives of oral biology","volume":"186 ","pages":"Article 106564"},"PeriodicalIF":2.1,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147388305","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}

{"title":"Generation and characterization of a murine amelogenesis imperfecta model","authors":"Eui-Sic Cho ,&nbsp;Jan C.-C. Hu ,&nbsp;Jung-Wook Kim","doi":"10.1016/j.archoralbio.2026.106563","DOIUrl":"10.1016/j.archoralbio.2026.106563","url":null,"abstract":"<div><h3>Objective</h3><div>Amelogenesis imperfecta (AI) refers to a group of rare yet complex genetic disorders that affect the quantity and/or quality of tooth enamel. Recently, in AI patients, we identified mutations that disrupt a conserved alternative splicing pattern of the <em>AMELX</em> gene, which encodes amelogenin, the most abundant enamel matrix protein. These mutations led to the retention of exon 4, which is normally skipped during the pre-mRNA splicing process, resulting in the characteristic pitted, hypoplastic, and hypomineralized enamel defects. To observe the impact of retention of exon 4 within <em>AMELX</em>, a gene edited knock-in mouse model was generated.</div></div><div><h3>Design</h3><div>A single-nucleotide knock-in mouse model was generated using CRISPR/Cas9 technology to introduce a silent mutation (NM_001415990.1: c.120 T&gt;C, p.(Ala40=)) that abrogated alternative splicing of exon 4. Following genomic sequence validation, the successfully-targeted mice were propagated, and their offspring genotyped for characterization. Micro-computed tomography analysis and immunohistochemistry analysis were performed on the hemi-mandibles of the wild-type and the knock-in mice.</div></div><div><h3>Results</h3><div>The enamel of the knock-in mice was chalky white and lacked translucency, due to faulty mineralization. This defective enamel broke down soon after tooth eruption. During the maturation stage, the ameloblast layer lost its cellular polarity and homogeneity, and intermingled with adjacent cell types to form disorganized clusters.</div></div><div><h3>Conclusions</h3><div>The validated and characterized <em>Amelx</em> c.120 T&gt;C mouse model provides a useful platform for investigating the molecular pathophysiology associated with retention of the exon 4 sequence. Following systemic characterization, this mouse model will serve as an important tool for assessing therapeutic strategies aimed at ameliorating the disease phenotype.</div></div>","PeriodicalId":8288,"journal":{"name":"Archives of oral biology","volume":"186 ","pages":"Article 106563"},"PeriodicalIF":2.1,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147370836","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}

{"title":"Exploring the effect of flavonoid-based solutions or formulations as antibiofilm agents in endodontics: A scoping review","authors":"Gabriel Pereira Nunes ,&nbsp;Elise Saint-Etienne ,&nbsp;Anna Carolina Volpi Mello-Moura ,&nbsp;Marcelle Danelon ,&nbsp;Torsten Sterzenbach ,&nbsp;Christian Hannig ,&nbsp;Cristiane Duque ,&nbsp;Renata Toledo Alves","doi":"10.1016/j.archoralbio.2026.106559","DOIUrl":"10.1016/j.archoralbio.2026.106559","url":null,"abstract":"<div><h3>Objective</h3><div>This scoping review aimed to map and summarize the evidence on the antimicrobial and antibiofilm efficacy of flavonoid-based solutions or formulations for endodontic applications.</div></div><div><h3>Design</h3><div>The review was conducted in accordance with the PRISMA-ScR guidelines. A comprehensive search was performed across databases for articles published up to April 2025. Eligible studies included those evaluating the antimicrobial effects of flavonoids on microorganisms associated with endodontic infections. Relevant data were extracted, and a descriptive synthesis of the findings was carried out.</div></div><div><h3>Results</h3><div>The results showed that fifteen studies met the inclusion criteria, demonstrating significant antimicrobial and antibiofilm activity of various flavonoids. Epigallocatechin-3-gallate was the most extensively studied compound, showing dose-dependent activity against <em>E. faecalis</em>, <em>F. nucleatum</em>, <em>A. israelii</em>, <em>S. mutans</em>, and <em>C. albicans</em>, with enhanced efficacy when combined with agents such as fosfomycin or the peptide KR-12-a5. Quercetin also displayed concentration-dependent antibiofilm effects and gene modulation in <em>E. faecalis</em>. Proanthocyanidin showed superior efficacy compared to conventional irrigants, especially at higher concentrations. Rutin, although limited in standalone efficacy, showed promising results when used as a photosensitizer. Other flavonoids such as apigenin, theaflavin, isoquercitrin, ampelopsin, chalcone, and chrysin also demonstrated varying degrees of antimicrobial activity, often similar to or surpassing conventional agents like chlorhexidine and calcium hydroxide in specific models.</div></div><div><h3>Conclusions</h3><div>Flavonoids exhibit significant potential as alternative or adjunctive agents for endodontic disinfection, especially in biofilm-related infections. Their efficacy is influenced by compound type, concentration, formulation, and synergistic combinations. Further research, especially clinical trials, is warranted to validate their therapeutic applicability and optimize delivery systems for clinical use in endodontics.</div></div>","PeriodicalId":8288,"journal":{"name":"Archives of oral biology","volume":"186 ","pages":"Article 106559"},"PeriodicalIF":2.1,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147370834","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}

{"title":"Long-term effects of altered functional demands induced by diet consistency throughout growth on adult rat masticatory muscle fibres","authors":"Maria-Zoi Theodoridou ,&nbsp;Aikaterini Lagou ,&nbsp;Aouatef Ait-Lounis ,&nbsp;Stavros Kiliaridis ,&nbsp;Gregory S. Antonarakis","doi":"10.1016/j.archoralbio.2026.106560","DOIUrl":"10.1016/j.archoralbio.2026.106560","url":null,"abstract":"<div><h3>Objective</h3><div>The functional profile and fibre characteristics of masticatory muscles may change depending on their functional demands. This in vivo experimental animal study aimed to evaluate the influence of diet consistency on fibre-type distribution and cross-sectional area in adult masticatory muscles using a rat model.</div></div><div><h3>Design</h3><div>Twenty-four male Wistar rats were divided into two groups of 12 and fed exclusively either a hard or soft diet following weaning. At 38 weeks, corresponding to adulthood, the masseter and digastric muscles were dissected. Immunofluorescence staining was performed to identify muscle fibre types (I, IIA, IIB, IIX), and morphometric analysis performed to measured fibre cross-sectional area and minimum diameter.</div></div><div><h3>Results</h3><div>In the masseter muscle, rats fed a soft diet exhibited a lower percentage of type IIA fibres (p = 0.006) and a higher percentage of type IIX fibres (p = 0.007) than rats fed a hard diet. No significant differences were found between groups in average fibre cross-sectional area or minimum diameter. In the digastric muscle, differences were detected only in fibre-size and not in fibre-type distribution. Rats fed a soft diet had larger average cross-sectional area and minimum diameter of type I fibres (p = 0.004; p = 0.003) and type IIB fibres (p = 0.007; p = 0.007) than those fed a hard diet.</div></div><div><h3>Conclusions</h3><div>Following soft-diet feeding, the masseter muscle was composed of less fast, fatigue-resistant fibre types (less IIA and more IIX). No such fibre-type distribution differences were observed in the digastric muscle, although some fibre types were larger in soft-diet-fed animals. These results indicate an adaptive response to reduced masticatory loading.</div></div>","PeriodicalId":8288,"journal":{"name":"Archives of oral biology","volume":"186 ","pages":"Article 106560"},"PeriodicalIF":2.1,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147373693","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}

{"title":"Corrigendum to “Evaluation of the effects induced by radiotherapy on dentin during endodontic instrumentation using a novel methodology for assessing wear resistance” [Archives of Oral Biology 183 (2026) Article Number 106493]","authors":"Leonardo Moreira Teodosio ,&nbsp;Ana Flavia Simões Barbosa ,&nbsp;Alexandra Mussolino de Queiroz ,&nbsp;Harley Francisco de Oliveira ,&nbsp;Camila Andrade Zamperini ,&nbsp;Jardel Francisco Mazzi-Chaves ,&nbsp;Manoel D. Sousa-Neto ,&nbsp;Yara Teresinha Corrêa Silva-Sousa ,&nbsp;Fuad Jacob Abi Rached-Junior ,&nbsp;Edson Alfredo ,&nbsp;Fabiane Carneiro Lopes-Olhê","doi":"10.1016/j.archoralbio.2026.106549","DOIUrl":"10.1016/j.archoralbio.2026.106549","url":null,"abstract":"","PeriodicalId":8288,"journal":{"name":"Archives of oral biology","volume":"185 ","pages":"Article 106549"},"PeriodicalIF":2.1,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146187506","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}

{"title":"Nature, nurture, or noise? Fluctuating asymmetry in permanent dentitions depends on trait plasticity and developmental timing","authors":"Emily Moes ,&nbsp;Heather JH Edgar","doi":"10.1016/j.archoralbio.2026.106540","DOIUrl":"10.1016/j.archoralbio.2026.106540","url":null,"abstract":"<div><h3>Objectives</h3><div>Dental fluctuating asymmetry (FA) is thought to reflect developmental instability. It has varied relationships with other early life measures of stress. We examine whether this variation is due to FA reflecting sensitive windows of development or susceptibility to disruption, based on the traits considered.</div></div><div><h3>Design</h3><div>Buccolingual and mesiodistal dimensions of all permanent teeth and molar intercuspal distances were measured from dental casts of 303 child participants of the Burlington Growth Study. Metric traits were aggregated into six discrete FA indices based on estimated age of trait development, trait susceptibility to environmental disturbances, or both. Early life biocultural factors were sourced from associated health history records and grouped into latent dimensions using factor analysis of mixed data. Using logistic regression, factors were then compared to all FA indices, separated by sex.</div></div><div><h3>Results</h3><div>Model outcomes varied by FA index and sex. FA indices that consisted of molar intercuspal measurements were significantly associated with biocultural latent factors, but only among females. No predictive relationships were found among male-specific models.</div></div><div><h3>Discussion</h3><div>Sensitive windows of development and differences in trait susceptibility to disruption are responsible for variation in dental FA of permanent teeth. Selecting traits with a high plastic component (such as molar intercuspal distances) rather than genetic component (crown dimensions) is critical to consider FA a metric of early life stress. Additional variability in dental FA, regardless of how it is measured, may be due to inherent “noise” in the developmental system.</div></div>","PeriodicalId":8288,"journal":{"name":"Archives of oral biology","volume":"185 ","pages":"Article 106540"},"PeriodicalIF":2.1,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146183867","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}

{"title":"Hesperetin modulates osteoprogenitor cells and macrophages under zoledronic acid and inflammatory stress","authors":"Igor Paulino Mendes Soares ,&nbsp;Owen Liepman ,&nbsp;Caroline Anselmi ,&nbsp;Sarah Chang ,&nbsp;Josimeri Hebling ,&nbsp;Renan Dal-Fabbro ,&nbsp;Marco C. Bottino","doi":"10.1016/j.archoralbio.2026.106538","DOIUrl":"10.1016/j.archoralbio.2026.106538","url":null,"abstract":"<div><h3>Objectives</h3><div>To investigate the osteogenic and immunomodulatory effects of hesperetin (HT) on alveolar bone-derived mesenchymal stem cells (aBMSCs) and macrophages under zoledronic acid (ZA) and inflammatory stress.</div></div><div><h3>Design</h3><div>aBMSCs were exposed to ZA (0–10 µM) for 3 days, followed by HT (0–1000 µM) for 3 days. Cell viability was assessed for 3 days of treatments, and osteogenic activity was evaluated by alizarin red quantification at 14 and 21 days. THP-1-derived macrophages were polarized to M1 using lipopolysaccharides (LPS, 1 µg/mL) and treated with HT (1–50 µM) to evaluate cell viability and synthesis of cytokines (ELISA). A co-culture system of aBMSCs and macrophages (1:1 ratio) was established under inflammatory stimulation (LPS ± 20 µM HT) to assess cell viability, cytokine release and mineralized matrix formation. Data were analyzed by ANOVA/post-hoc tests (α = 5 %).</div></div><div><h3>Results</h3><div>ZA significantly reduced aBMSCs viability and mineralization in a dose-dependent manner. HT (5–50 µM) enhanced mineralization in healthy aBMSCs and partially restored it after ZA exposure. In M1 macrophages, HT (5–20 µM) decreased TNF-α, IL-1α, and IL-6 synthesis without affecting viability. In inflammatory co-cultures, HT (20 µM) preserved cell viability, increased mineralized matrix deposition, and reduced cytokine release compared to LPS-only controls.</div></div><div><h3>Conclusions</h3><div>This study evidenced that HT can concurrently stimulate osteogenic differentiation and suppress inflammatory responses under ZA- and LPS-induced stress. HT emerges as a promising osteoimmunomodulatory adjuvant to enhance bone regeneration and mitigate bisphosphonate-related osteonecrosis.</div></div>","PeriodicalId":8288,"journal":{"name":"Archives of oral biology","volume":"185 ","pages":"Article 106538"},"PeriodicalIF":2.1,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146168508","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}

{"title":"Substance P involvement in the interaction between Streptococcus mutans and human aortic endothelial cells","authors":"Takahiko Oho ,&nbsp;Emi Nagata ,&nbsp;Naofumi Tamaki","doi":"10.1016/j.archoralbio.2026.106537","DOIUrl":"10.1016/j.archoralbio.2026.106537","url":null,"abstract":"<div><h3>Objectives</h3><div><em>Streptococcus mutans</em>, a causative organism of dental caries, has also been implicated in the pathogenesis of cardiovascular disease (CVD). Substance P (SP) involvement in physiological and pathological processes within the cardiovascular system is currently the foci of research. The role of SP in modulating the human aortic endothelial cells (HAECs) response to <em>S. mutans</em> within the context of CVD pathogenesis has not been examined. This study aimed to investigate SP expression in <em>S. mutans</em>-stimulated HAECs and to clarify the role of SP in the interaction between <em>S. mutans</em> and HAECs, considering its cooperative action with an innate immune factor DMBT1.</div></div><div><h3><em>Design:</em></h3><div>HAECs were stimulated with <em>S. mutans</em> strains. SP expression was analyzed by dot blot assay and RT-PCR. <em>S. mutans</em> binding to SP was determined using ELISA. <em>S. mutans</em> aggregation was evaluated by monitoring decrease in optical density and phase-contrast microscopy. Effects of SP and/or DMBT1 on the interaction between <em>S. mutans</em> and HAECs were examined by invasion assay, cytokine assay, and cytotoxicity assay.</div></div><div><h3>Results</h3><div>All tested <em>S. mutans</em> strains induced SP production in HAECs. <em>S. mutans</em> bound directly to SP. SP agglutinated <em>S. mutans</em> and pronounced aggregation was induced by SP when used with DMBT1. SP reduced <em>S. mutans</em> invasion of HAECs, suppressed <em>S. mutans</em>-induced cytokine production in HAECs, and decreased <em>S. mutans</em>-mediated cytotoxicity to HAECs. These inhibitory effects of SP were further enhanced by DMBT1.</div></div><div><h3>Conclusion</h3><div>These findings suggest that SP, acting in concert with DMBT1, exerts a protective role against <em>S. mutans</em>-induced CVD processes in HAECs.</div></div>","PeriodicalId":8288,"journal":{"name":"Archives of oral biology","volume":"184 ","pages":"Article 106537"},"PeriodicalIF":2.1,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146133912","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}

{"title":"Cellular passages modulate pre-osteoblast responses to bisphosphonate in high-passage cell models","authors":"Charukrit Lilakhunakon ,&nbsp;Somying Patntirapong","doi":"10.1016/j.archoralbio.2026.106521","DOIUrl":"10.1016/j.archoralbio.2026.106521","url":null,"abstract":"<div><h3>Objective</h3><div>This study examined the effects of cell passages, drug treatment, or interaction between cell passage and drug treatment on pre-osteoblast growth and activities.</div></div><div><h3>Design</h3><div>Pre-osteoblasts, MC3T3-E1, were subcultured until reaching high passages (passage 42; P42) and late passages (passage 62; P62). Cells were treated with oral bisphosphonate (BP), alendronate (ALN), at concentrations 1 and 5 μM. Cells were evaluated and compared for cell survival, migration, adhesion, actin cytoskeleton, cell spreading, and gene expressions.</div></div><div><h3>Results</h3><div>Two-way ANOVA showed that cell migration, cytoskeleton, nuclear condensation, and Intβ1 gene expression were impacted by the interaction between cell passage and ALN, while cell growth, death, adhesion, and spreading were affected by either cell passage or ALN. Cell growth was inhibited by cell passage and ALN. ALN at 5 μM (A5) increased cell death in P42. Cell adhesion was reduced in P62 compared to P42 in A1 condition. Higher cell passage and ALN promoted detachment under mechanical stress. Cell spreading was also disrupted by ALN. Adhesion-related gene expressions such as Intβ1 and FAK were downregulated by cell passage in A5 treatment.</div></div><div><h3>Conclusion</h3><div>These findings demonstrated differential cellular responses to BPs based on cell passage and interaction between cell passage and ALN. High and late passage cells exhibited distinct sensitivities and behaviors. This underscores the importance of using higher-passage cell models to better mimic aged osteoblasts <em>in vitro</em> when evaluating preclinical studies.</div></div>","PeriodicalId":8288,"journal":{"name":"Archives of oral biology","volume":"184 ","pages":"Article 106521"},"PeriodicalIF":2.1,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146036885","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}