Molecular Oral Microbiology最新文献

{"title":"Defense Systems and Prophage Detection in Streptococcus mutans Strains.","authors":"Olivier Claisse, Cas Mosterd, Claire Le Marrec, Johan Samot","doi":"10.1111/omi.70014","DOIUrl":"10.1111/omi.70014","url":null,"abstract":"<p><p>Although the species is extensively studied, limited data are available on antiphage defense systems (APDSs) in Streptococcus mutans. The present study aimed to explore the diversity and the occurrence of APDSs and to search for prophages in the genomes of clinical isolates of S. mutans using bioinformatics tools. Forty-four clinical isolates of S. mutans were obtained from saliva samples of people with Parkinson's disease. Genomic DNA was extracted, sequenced using Illumina MiSeq technology, and analyzed for the presence of defense systems using DefenseFinder and PADLOC. CRISPR-Cas systems were characterized using CRISPRCasFinder, and prophages were detected by the PhiSpy pipeline from RAST. AcrFinder and AcrHub were used to identify anti-CRISPR proteins. Each strain harbored between 6 and 12 APDS, with restriction-modification systems being the most prevalent, followed by the MazEF toxin-antitoxin system and CRISPR-Cas systems. Type II-C CRISPR-Cas systems were not identified here in S. mutans. Novel variations in type II-A signature protein Cas9 were identified, allowing their classification into four distinct groups. Variability in direct repeat sequences within the same CRISPR array was also observed, and 80% of the spacers were classified as targeting \"dark matter\". A unique prophage, phi_37bPJ2, was detected, showing high similarity with previously described phages. The AcrIIA5 protein encoded by phi_37bPJ2 was conserved and suggested to remain functionally active. This study reveals the diversity of APDSs in S. mutans and the limited presence of prophages. The findings provide a foundation for future research on the evolutionary dynamics of these systems and their role in S. mutans adaptation to phage pressure.</p>","PeriodicalId":18815,"journal":{"name":"Molecular Oral Microbiology","volume":" ","pages":"57-68"},"PeriodicalIF":2.9,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12964521/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145489363","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"UCHL1 Exacerbates Periodontitis by Coordinating Mitochondrial Dysfunction and Endoplasmic Reticulum Stress in Macrophages.","authors":"Yun Yuan, Shengjia Ye, Hanxiao Xue, Xiayue Jin, Xueying Yang, Hongming Zhang, Hui Huang","doi":"10.1111/omi.70028","DOIUrl":"https://doi.org/10.1111/omi.70028","url":null,"abstract":"<p><strong>Background: </strong>Given the pivotal role of macrophages in both the progression and regenerative phases of periodontitis, targeting macrophage-mediated immunity represents a novel therapeutic strategy for periodontitis management. Ubiquitin carboxyl-terminal hydrolase L1 (UCHL1) has been previously implicated in inflammatory processes. However, how UCHL1 regulates macrophage immune response in periodontitis remains to be elucidated.</p><p><strong>Methods: </strong>Ligature-induced periodontitis mice and Porphyromonas gingivalis lipopolysaccharide (P.g LPS) were used to investigate the expression of UCHL1 in macrophages during immune responses. Lentivirus and an inhibitor were conducted to determine the role of UCHL1 in the periodontitis-associated macrophage immune response. The mitochondrial function and the endoplasmic reticulum status of macrophages were examined to elucidate the underlying mechanisms. Finally, we constructed hydrogels containing UCHL1 inhibitor and evaluated their efficacy in treating periodontitis.</p><p><strong>Results: </strong>The expression of UCHL1 was upregulated in proinflammatory immune response of periodontitis-associated macrophages. Inhibition of UCHL1 reduced the expression and release of TNF-α, IL-6, and IL-1β. In addition, inhibition of UCHL1 in macrophages improved the osteogenesis and migration ability of MC3T3-E1 cells in the co-culture system. Mechanistically, inhibition of UCHL1 ameliorated LPS-induced mitochondrial damage and endoplasmic reticulum stress in macrophages. LDN@GelMA hydrogel had great in vitro anti-inflammatory and bone-promoting effects. Periodontal injection of LDN@GelMA hydrogel alleviated local inflammation and promoted alveolar bone regeneration.</p><p><strong>Conclusions: </strong>Our data suggest that UCHL1 may serve as a critical negative regulator for periodontitis treatment, and inhibition of UCHL1 is expected to improve the periodontal inflammatory microenvironment and promote alveolar bone regeneration.</p>","PeriodicalId":18815,"journal":{"name":"Molecular Oral Microbiology","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147593196","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ginsenoside Compound K Plays an Anti-Inflammatory Role in Gingival Epithelial Cells Stimulated With Porphyromonas gingivalis by Regulating Pyruvate Kinase M2.","authors":"Luxin Jin, Lin Lu, Yang Jiao, Yanchun Wang, Hongbing He","doi":"10.1111/omi.70029","DOIUrl":"https://doi.org/10.1111/omi.70029","url":null,"abstract":"<p><strong>Background: </strong>Globally prevalent periodontitis, an inflammatory disease, may be associated with glucose metabolism disorders. Pyruvate kinase M2 (PKM2), the key enzyme of glycolysis, is potentially implicated in periodontitis pathogenesis, although its precise role is unclear. Ginsenoside compound K (CK) has strong anti-inflammatory effects. Prior studies indicate that CK down-regulates PKM2 expression, yet it remains unclear whether CK can regulate PKM2 to modulate the inflammatory response. Furthermore, CK's role in periodontitis lacks pharmacological investigation.</p><p><strong>Methods: </strong>A periodontitis cell model was established by stimulating human gingival epithelial cells (HGECs) with Porphyromonas gingivalis (Pg), and subsequently intervened with CK. Western blotting assessed the expressions of PKM2, phospho-PKM2 (Tyr105), nuclear factor kappa-B P65 (NF-κB P65), and phosphorylated NF-κB p65 (Ser536). Enzyme-linked immunosorbent assay measured interleukin 1β (IL-1β) and tumor necrosis factor-α (TNF-α) levels in culture supernatants.</p><p><strong>Results: </strong>Pg stimulation induced NF-κB p65 (Ser536) activation and the secretion of IL-1β and TNF-α in HGECs and promoted PKM2 (Tyr105) phosphorylation. PKM2 was found to be the upstream regulator of NF-κB p65, and NF-κB p65 activated PKM2 through positive feedback to promote IL-1β and TNF-α production, forming a feedback regulatory loop. CK inhibited Pg-induced inflammation and NF-κB p65 (Ser536) and PKM2 (Tyr105) phosphorylation in HGECs. Furthermore, PKM2 overexpression significantly reversed CK's anti-inflammatory effects.</p><p><strong>Conclusions: </strong>The PKM2/NF-κB p65 pathway is involved in regulating the expression of inflammatory cytokines in Pg-stimulated HGECs and serves as a crucial inflammatory regulatory pathway in the Pg-stimulated HGECs model. CK exhibits anti-inflammatory activity by inhibiting the PKM2-mediated NF-κB signaling pathway and has potential as PKM2 modulator for treating periodontitis and other inflammatory diseases.</p>","PeriodicalId":18815,"journal":{"name":"Molecular Oral Microbiology","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147593201","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neutrophil Activation Decreases Ability to Kill Oral Streptococcus gordonii.","authors":"Kiana T Bynum, Michelle Panasiewicz, Jason G Kay","doi":"10.1111/omi.70019","DOIUrl":"10.1111/omi.70019","url":null,"abstract":"<p><p>As first responders, neutrophils are a vital component of the host defense against oral pathogens, and their function is critical in preventing the progression of periodontal diseases. Streptococcus gordonii, a generally commensal oral bacterium, has been implicated in the pathogenesis of diseases by operating as a pathobiont with Porphyromonas gingivalis in periodontitis, and as an independent pathogen in infective endocarditis. Although the pathogenicity of S. gordonii is variable, its role in modulating, as well as responding to, host neutrophils remain, poorly understood. This study focuses on neutrophil activation, migration, and bactericidal activity towards S. gordonii. Our results found S. gordonii induced significant upregulation of surface markers CD63 and CD66 on neutrophils, a phenotypic change reminiscent of an oral neutrophil, and was enhanced by pre-activation of neutrophils by lipopolysaccharide (LPS) or the oral pathogen P. gingivalis. Co-incubations with P. gingivalis also led to a decreased ability of neutrophils to kill the normally commensal S. gordonii, though not other commensals with opportunistic pathogen potential, including Escherichia coli or Staphylococcus aureus. This increase in survival correlated with changes in phagosomal maturation, a decrease in cytoplasmic and phagosomal-associated granules, and increased IL-1β production. These results suggest oral streptococci may significantly contribute to oral neutrophil phenotypes associated with health, but introduction of oral pathogens can exacerbate a neutrophil shift and contribute to the persistence of S. gordonii, and its ability to contribute to the pathogenesis of periodontal disease.</p>","PeriodicalId":18815,"journal":{"name":"Molecular Oral Microbiology","volume":" ","pages":"94-106"},"PeriodicalIF":2.9,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12990969/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145857119","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Expanded Functional Characterization and Optimization of Protein Expression in Treponema denticola Shuttle Plasmids.","authors":"M Paula Goetting-Minesky, Valentina Godovikova, Prakaimuk Saraithong, Alexander H Rickard, Brigette R Crawley, Sara M Agolli, Reagan L Boyce, Trishna L Appaji, J Christopher Fenno","doi":"10.1111/omi.70016","DOIUrl":"10.1111/omi.70016","url":null,"abstract":"<p><p>Oral spirochetes are among the small group of keystone pathogens contributing to dysregulation of periodontal tissue homeostasis, leading to breakdown of the tissue and bone supporting the teeth in periodontal disease. Of the more than 60 oral Treponema species and phylotypes, Treponema denticola is one of the few that can be grown in culture and the only one in which genetic manipulation is practicable. T. denticola is thus a model organism for studying spirochete behavior, metabolism, and interactions with other microbes and host tissues that are relevant to oral diseases. We recently demonstrated enhanced transformation efficiency using a synthetic shuttle plasmid resistant to T. denticola restriction-modification systems. Here, we report further optimization of the shuttle plasmid system by minimizing its size and by characterizing an array of promoter-gene constructs for plasmid-based genetic complementation, including the first inducible system for controlled expression of potentially toxic plasmid-encoded genes in Treponema. Our results highlight the importance of precise pairing of promoters and genes of interest for obtaining biologically optimal protein expression. This work expands the utility of the T. denticola shuttle plasmid system and will facilitate future studies in the analysis of Treponema physiology and behavior. Rigorous genetic analysis in oral spirochetes has been hampered by the limited utility of available versions of the Escherichia coli-T. denticola shuttle plasmid system. We report expanded characterization, refinement, and minimization of the shuttle plasmid, including relative activity of diverse promoters and the first inducible expression system described for T. denticola. We show that careful customization of the shuttle plasmid for specific applications is crucial for obtaining successful results.</p>","PeriodicalId":18815,"journal":{"name":"Molecular Oral Microbiology","volume":" ","pages":"69-84"},"PeriodicalIF":2.9,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12878829/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145636239","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Differences Between Oral Neutrophils and Neutrophils Isolated From the Blood of Healthy Donors.","authors":"Svetlana N Pleskova, Nikolay A Bezrukov, Ekaterina D Nikolaeva, Yulia A Zamazkina","doi":"10.1111/omi.70025","DOIUrl":"https://doi.org/10.1111/omi.70025","url":null,"abstract":"<p><p>The morphological and viscoelastic properties of blood neutrophils and neutrophils isolated from the oral cavity of the same donor were compared using scanning ion conductance microscopy. It was found that cell morphology, including morphometric parameters (height, diameter, and cell volume), did not differ significantly. However, the elasticity of the membrane-cytoskeletal complex was primarily determined by the cell compartment and its functional state (e.g., migration or adhesion) rather than the neutrophils' ecological niche (blood or oral cavity). The ability of blood neutrophils and oral neutrophils to produce reactive oxygen species (ROS) was assessed using luminol-dependent chemiluminescence. Neutrophils isolated from the oral cavity demonstrated a significantly higher ROS-producing activity compared to blood neutrophils from the same donor. Additionally, oral neutrophils exhibited high variability in ROS production levels, even within the same donor on different days of collection. When comparing the stimulation of ROS production in blood and oral neutrophils exposed to S. aureus 2879M, the cells displayed opposing responses: blood neutrophils were stimulated by Staphylococci, whereas oral neutrophils were inhibited. This response persisted when cells were stimulated by Staphylococci preincubated with saliva. The sequential addition of unfiltered saliva to neutrophils and Staphylococci enhanced this trend, while filtered oral fluid attenuated it. For the first time, it was established that saliva without bacteria (filtered through bacterial filters) suppresses the production of ROS by both blood neutrophils and oral neutrophils, most likely indicating an anti-inflammatory effect of saliva.</p>","PeriodicalId":18815,"journal":{"name":"Molecular Oral Microbiology","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2026-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147355757","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Oral Microbiota, Its Evolution, and Aspects of Support for Oral Health.","authors":"Svetlana Pleskova, Nikolay Bezrukov","doi":"10.1111/omi.70011","DOIUrl":"10.1111/omi.70011","url":null,"abstract":"<p><p>Over the years, humanity has accumulated knowledge about the pathogens of infectious diseases and the ability of the human body to resist external aggression. In the last century, it became clear that the normal microflora of the human body can be used as an ally to resist a whole range of diseases. However, the intestinal microflora is the main object of modern complex studies. This review focuses on the microflora of the oral cavity. It describes the main microbiological composition of the microflora, including the most important bacterial species, fungi, and viruses. The main factors influencing the emergence of balance in the system \"human oral cavity-microorganisms\" are considered as well as environmental features that affect the formation of the species composition. The main functions performed by the oral microflora are described. Possible mechanisms for correcting initial dysbiotic disorders are also considered, including probiotics, bacteriophages, gases and thermotherapy, photobiomodulation, and diet correction.</p>","PeriodicalId":18815,"journal":{"name":"Molecular Oral Microbiology","volume":" ","pages":"1-25"},"PeriodicalIF":2.9,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145345763","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Long Noncoding RNA Malat1 and Neat1 Associated With Dysbiotic Microbiome and Epithelial-Mesenchymal Transition in Periodontitis.","authors":"Saif M Al-Mufti, Ali A Abdulkareem, Nibras H Chasib, Mike Milward, Paul R Cooper","doi":"10.1111/omi.70010","DOIUrl":"10.1111/omi.70010","url":null,"abstract":"<p><strong>Introduction: </strong>The regulatory mechanisms of epithelial-mesenchymal transition (EMT) involved in periodontitis pathogenesis are poorly understood. Consequently, this study aimed to investigate the association of the long noncoding (lnc) RNAs, NEAT1 and MALAT1, with EMT in periodontitis.</p><p><strong>Methods: </strong>Gingival tissue samples (n = 57) were obtained from periodontitis patients indicated for surgical treatment and healthy control individuals. Full mouth periodontal charting was recorded for all patients together with collection of subgingival biofilm samples to determine bacterial load for key-periodontal pathogens. Histopathological analysis was used to assess inflammatory cell infiltration, and RT-qPCR analysis was performed to quantify the expression of the key EMT biomarkers of E-cadherin, β-catenin, Snail1 and vimentin, and the lncRNAs of Neat1 and Malat1.</p><p><strong>Results: </strong>The clinical parameters and percentage of inflammatory cell infiltration were significantly higher in the periodontitis group compared with healthy controls. In periodontitis, expressions of Malat1 and E-cadherin were significantly downregulated, whereas Neat1, Snail1 and vimentin were significantly upregulated in comparison to controls. Receiver-operating characteristic (ROC) analyses demonstrated moderate-to-good diagnostic accuracy of Neat1, Malat1, Snail1, E-cadherin and vimentin (area under the curve [AUC]: 70.3%, 67.5%, 78.7%, 89.9% and 74.3%, respectively) to discriminate periodontal health from disease.</p><p><strong>Conclusion: </strong>Probing pocket depth, bleeding scores, expression of Neat1, red complex bacteria (Porphyromonas gingivalis and Treponema denticola) and downregulation of Malat1 and E-cadherin were strongly associated with EMT. Data also highlighted an association between Neat1 and Malat1 with the induction of the EMT phenotype in periodontitis, and these lncRNAs may therefore provide novel diagnostic biomarkers.</p>","PeriodicalId":18815,"journal":{"name":"Molecular Oral Microbiology","volume":" ","pages":"38-47"},"PeriodicalIF":2.9,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145275396","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genomic Insights Into the Treponema Genus: Taxonomic Resolution of Treponema vincentii and Description of Two Novel Species, Treponema plautii sp. nov. and Treponema sinense sp. nov.","authors":"Jordan Y H Fong, Man Lung Yeung, Tsz Tuen Li, Wing Ho Li, Yuanchao Ma, Yan Zhao, Wai Keung Leung, Jade L L Teng","doi":"10.1111/omi.70009","DOIUrl":"10.1111/omi.70009","url":null,"abstract":"<p><strong>Objectives: </strong>Periodontal disease, a global health concern, is strongly associated with oral treponemes. However, the taxonomy of some species remains unresolved, hindering our understanding of their roles in disease. This study aims to clarify the taxonomy of three strains isolated from patients with periodontal disease using phylogenomic and comparative genomic analyses.</p><p><strong>Materials and methods: </strong>We performed genome sequencing for OMZ 800 and conducted phylogenomic and comparative genomic analyses of multiple strains to clarify their taxonomy.</p><p><strong>Results: </strong>Phylogenomic and in-silico genome comparisons confirmed OMZ 800 as \"T. vincentii\" (Average Nucleotide Identity [ANI]>95%). We designated OMZ 800^T as the type strain for T. vincentii to establish its official standing in bacterial taxonomy. OMZ 806 (2.7 Mb, 44.9% GC) clustered with phylogroup IB strain (ANI>95% vs. OMZ 305), whereas OMZ 838 (2.7 Mb, 44.6% GC) clustered with phylogroup IA strains (ANI>95% vs. OMZ 855 and OMZ 857). Both OMZ 806 and OMZ 838 strains showed ANI<95% compared to T. medium ATCC700293^T, supporting their classification as novel species. We propose Treponema plautii sp. nov. OMZ 806^T (with OMZ305 as additional strain) and Treponema sinense sp. nov. OMZ 838^T (with OMZ 855 and OMZ 857 as additional strains).</p><p><strong>Conclusion: </strong>This study clarifies Treponema taxonomy by designating OMZ 800^T as the type strain of T. vincentii and proposing two novel species, providing a refined taxonomical framework for this important genus.</p>","PeriodicalId":18815,"journal":{"name":"Molecular Oral Microbiology","volume":" ","pages":"26-37"},"PeriodicalIF":2.9,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12781046/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145054519","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Apelin-12 Attenuates LPS-Induced Cellular Senescence in Human Dental Pulp Cells via SIRT6-Mediated Pathways: Implications for Gingivitis Management.","authors":"Lin Zhang, Dan Luo, Li Bai","doi":"10.1111/omi.70012","DOIUrl":"10.1111/omi.70012","url":null,"abstract":"<p><p>Microbial infections and lipopolysaccharide (LPS)-induced senescence in human dental pulp cells (hDPCs) play a significant role in gingivitis etiology. However, the role of Apelin-12 in oral diseases, particularly its modulation of cellular senescence, remains poorly understood. This study investigated the protective effects of Apelin-12 against LPS-induced cellular senescence in hDPCs and its underlying mechanisms using cell isolation, culture, treatment, and transduction techniques, combined with reverse transcription-polymerase chain reaction (RT-PCR), Western blotting, telomerase activity assays, senescence-associated β-galactosidase (SA-β-Gal) staining, and gene silencing. We first confirmed apelin receptor (APJ) expression in hDPCs and found that LPS significantly downregulated APJ at both mRNA and protein levels. Apelin-12 treatment restored telomerase activity and upregulated human telomerase reverse transcriptase (hTERT), while reducing senescence markers, including γH2AX and SA-β-Gal. Additionally, Apelin-12 suppressed the expression of senescence regulators p21 and acetylated p53 (ac-p53). Mechanistically, Apelin-12 restored SIRT6 (but not SIRT1) expression, and silencing SIRT6 abolished its anti-senescence effects, as evidenced by elevated p21, ac-p53, and SA-β-Gal, along with reduced hTERT and telomerase activity. These findings demonstrate that Apelin-12 attenuates LPS-induced cellular senescence in hDPCs via SIRT6-mediated pathways, suggesting its therapeutic potential for gingivitis management.</p>","PeriodicalId":18815,"journal":{"name":"Molecular Oral Microbiology","volume":" ","pages":"48-56"},"PeriodicalIF":2.9,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145318459","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}