Madeline X F Kosho, Alessio Ciurli, Martin Giera, Jacques Neefjes, Bruno G Loos
{"title":"Metabolomic Profiles of Oral Rinse Samples to Distinguish Severe Periodontitis Patients From Non-Periodontitis Controls.","authors":"Madeline X F Kosho, Alessio Ciurli, Martin Giera, Jacques Neefjes, Bruno G Loos","doi":"10.1111/jre.13379","DOIUrl":"https://doi.org/10.1111/jre.13379","url":null,"abstract":"<p><strong>Aims: </strong>To explore the potential of metabolomic profiles of oral rinse samples to distinguish between patients with severe periodontitis (stage III/IV) and non-periodontitis controls. This is coupled to an analysis of differences in metabolomic profiles between individuals without periodontitis, patients with localized periodontitis, and patients with generalized periodontitis.</p><p><strong>Methods: </strong>Periodontitis patients and controls were recruited, all aged ≥ 40 years. Study participants were asked to rinse vigorously for 30 s with 10 mL phosphate buffered saline. Metabolites were identified using a semi-targeted liquid chromatography tandem mass spectrometry (LC-MS/MS) platform.</p><p><strong>Results: </strong>In total, 38 periodontitis patients (18 localized, 20 generalized stage III/IV periodontitis patients) and 16 controls were included. Metabolomic profiles of oral rinse samples were able to distinguish patients with severe periodontitis (stage III/IV) from non-periodontitis controls. Among various variables for the severity of periodontitis, we found that the number of sites with deep pockets (PPD) ≥ 6 mm explained best the differences in metabolomic profiles between controls and patients with severe periodontitis. Subjects with a high number of sites with PPD ≥ 6 mm were characterized by a higher level of phosphorylated nucleotides, amino acids, peptides, and dicarboxylic acids. Metabolomic profiles were also significantly different between controls vs. generalized periodontitis and between localized periodontitis vs. generalized periodontitis (p < 0.05).</p><p><strong>Conclusion: </strong>Our study demonstrates that simply collected oral rinse samples are suitable for LC-MS/MS based metabolomic analysis. We show that a metabolomic profile with a substantial number of metabolites can distinguish severe periodontitis patients from non-periodontitis controls. These observations can be a basis for further studies into screening to identify subjects with the risk of having severe periodontitis.</p>","PeriodicalId":16715,"journal":{"name":"Journal of periodontal research","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143623416","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}
Dimitris Sokos, Marja L Laine, Elena A Nicu, Kelly Hiu Lam Chung, Ni-Ni Dong Qing Sluijk, Dagmar Else Slot, Sergio Bizzarro
{"title":"Periodontitis and Platelets Status: A Systematic Review With Meta-Analysis and Trial Sequential Analysis.","authors":"Dimitris Sokos, Marja L Laine, Elena A Nicu, Kelly Hiu Lam Chung, Ni-Ni Dong Qing Sluijk, Dagmar Else Slot, Sergio Bizzarro","doi":"10.1111/jre.13398","DOIUrl":"https://doi.org/10.1111/jre.13398","url":null,"abstract":"<p><strong>Aim: </strong>Circulating platelets are essential in hemostasis, thrombosis, and immune responses. Modifications in platelet function may impact immunological reactions to dental biofilm and cardiovascular health. Understanding changes in platelet status and activity in patients with periodontitis is still a subject of investigation. This study aimed to synthesize evidence from observational studies that investigated platelet status and activity in patients with and without periodontitis.</p><p><strong>Methods: </strong>MEDLINE-PubMed, EMBASE, and Cochrane-CENTRAL Library databases were searched up to November 2024. Primary outcomes included platelet count (PC) and mean platelet volume (MPV). Secondary outcomes encompassed any other biomarker relevant to platelet status and activity. Methodological quality was evaluated using the Newcastle-Ottawa scale, and heterogeneity was analyzed. Descriptive analysis of outcomes and meta-analysis, incorporating trial sequential analysis of PC and MPV, were conducted. The body of evidence was graded by utilizing the Grading of Recommendations Assessment, Development, and Evaluation (GRADE).</p><p><strong>Results: </strong>3621 unique records were identified, resulting in 23 eligible studies with 22 variables evaluating the platelet status. Fourteen studies exhibited a low risk of bias, and 9 exhibited moderate risk of bias. PC in patients with periodontitis was significantly higher compared to individuals without periodontitis (Mean Difference (MD) = 23.55 ×10<sup>9</sup>/L, 95% CI [7.68; 39.43]). There was no statistically significant difference between the groups for MPV (MD = 0.16 fL, 95% CI [-0.49; 0.82]). Trial sequential analysis indicated a conclusive meta-analysis of PC and highlighted the need for additional data on MPV from future trials.</p><p><strong>Conclusions: </strong>The certainty is moderate for slightly higher PC in patients with periodontitis compared to individuals without it and low for no difference in MPV between the two groups. The evidence is not robust to claim a clear difference in other platelet activation biomarkers between the two groups.</p><p><strong>Trial registration: </strong>International Prospective Register of Systematic Reviews (PROSPERO) by number: CRD42023439051.</p>","PeriodicalId":16715,"journal":{"name":"Journal of periodontal research","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143605251","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}
Leandro Machado Oliveira, Thayná Regina Pelissari, Carlos Heitor Cunha Moreira, Karla Zanini Kantorski, Raquel Pippi Antoniazzi, Fabrício Batistin Zanatta
{"title":"Early Cigarette Smoking Onset Increases Edentulism Risk.","authors":"Leandro Machado Oliveira, Thayná Regina Pelissari, Carlos Heitor Cunha Moreira, Karla Zanini Kantorski, Raquel Pippi Antoniazzi, Fabrício Batistin Zanatta","doi":"10.1111/jre.13399","DOIUrl":"https://doi.org/10.1111/jre.13399","url":null,"abstract":"<p><p>Adults who began smoking regularly in early childhood (before 10 years) face an especially high risk of edentulism if they continue smoking into adulthood. Comprehensive tobacco control policies should target early childhood, ultimately contributing to the prevention of subsequent edentulism and other noncommunicable diseases.</p>","PeriodicalId":16715,"journal":{"name":"Journal of periodontal research","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143573321","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}
Daniele Cardaropoli, Mauricio Araujo, Daniel Buser, Ueli Grunder, Joseph Kan, Robert A Levine, Mariano Sanz, Giovanni Zucchelli, Otto Zuhr, Søren Jepsen
{"title":"Treatment Options for the Management of the Postextraction Socket: Report From the First Giuseppe Cardaropoli Foundation Consensus Conference.","authors":"Daniele Cardaropoli, Mauricio Araujo, Daniel Buser, Ueli Grunder, Joseph Kan, Robert A Levine, Mariano Sanz, Giovanni Zucchelli, Otto Zuhr, Søren Jepsen","doi":"10.1111/jre.13385","DOIUrl":"https://doi.org/10.1111/jre.13385","url":null,"abstract":"<p><strong>Aim: </strong>Different approaches have been proposed for implant placement following tooth extraction. A Consensus conference was organised to provide expert-based recommendations for the treatment of the postextraction site in the aesthetic zone in conjunction with implant therapy.</p><p><strong>Methods: </strong>A panel of eight experts with a documented longstanding clinical and research experience in the field of implant therapy in the aesthetic zone were invited to participate in a structured survey. Participants were asked to select their preferred treatment approach for different clinical scenarios of the postextraction site from a list of different treatment options. Results were summarised and discussed in person at a 2 day consensus conference. Based on the outcome, treatment recommendations were phrased and are reported here.</p><p><strong>Results: </strong>The group agreed that in case of an intact alveolus, immediate implant placement with immediate prosthetics represents the reference choice if proper primary stability can be achieved and the buccal bone plate is present. A bone-to-implant gap more than 2 mm should be seeked and grafted. Alveolar ridge preservation and early placement with contour augmentation may represent an alternative. If the alveolus is compromised, a staged approach (early or delayed placement) with bone augmentation may be preferred.</p><p><strong>Conclusions: </strong>The characteristics of the site, in terms of the available bone volume, the integrity of the buccal bone plate and the periodontal phenotype are determining factors in the therapeutic choice. Therefore, case selection based on well-defined selection criteria is extremely important and is the adequate way to guide the clinician in choosing the most appropriate approach to postextraction site management and timing for implant placement.</p>","PeriodicalId":16715,"journal":{"name":"Journal of periodontal research","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143501998","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":"Xanthine Derivative KMUP-3 Alleviates Periodontal Bone Resorption by Inhibiting Osteoclastogenesis and Macrophage Pyroptosis.","authors":"Shang-En Huang, Kai-Fang Hu, Meng-Xuan Lin, Ching-Jiunn Tseng, Bin-Nan Wu, Zen-Kong Dai, Jong-Hau Hsu, Jwu-Lai Yeh","doi":"10.1111/jre.13393","DOIUrl":"https://doi.org/10.1111/jre.13393","url":null,"abstract":"<p><strong>Aim: </strong>This study investigated the function effects of KMUP-3, a self-developed synthetic xanthine-based derivative, in suppressing Porphyromonas gingivalis (Pg-LPS)-aggravated osteoclastogenesis and pyroptosis as a potential treatment for periodontitis.</p><p><strong>Methods: </strong>In vitro, the effects of Pg-LPS and KMUP-3 on osteoclast formation and macrophage pyroptosis were investigated using the receptor activator of nuclear factor-κB ligand (RANKL)-primed RAW264.7 macrophages. In vivo, the therapeutic effects of KMUP-3 were evaluated in a model of experimental periodontitis induced by gingival ligature placement.</p><p><strong>Results: </strong>We reveal that KMUP-3 suppressed osteoclastogenesis, inducible nitric oxide synthase activation, and reduced nitric oxide production enhanced by Pg-LPS in RANKL-primed RAW264.7 cells while also decreasing TLR4/NF-κB p65 pathway activation and decreased pro-inflammatory cytokine production; moreover, Pg-LPS promoted NLRP3 activation and exacerbated pyroptosis induction effects that were abolished by KMUP-3. Finally, KMUP-3 ameliorated alveolar bone loss and IL-1β levels in the gingival crevicular fluid in the rat ligature periodontitis model.</p><p><strong>Conclusions: </strong>Our study demonstrated that KMUP-3 attenuates Pg-LPS-enhanced osteoclastogenesis and macrophage pyroptosis. Notably, KMUP-3 alleviates alveolar bone loss in experimental periodontitis rats and thus suggests its certain role in safeguarding against periodontal bone resorption.</p>","PeriodicalId":16715,"journal":{"name":"Journal of periodontal research","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143502020","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":"Toll-Like Receptor 7 Promotes Periodontal Inflammation and Alveolar Bone Resorption Through the NF-κB Signaling Pathway.","authors":"Rui Jing, Jiawei Lu, Ruiling Wang, Zehui Xiong, Yanan Yang, Lijun Luo","doi":"10.1111/jre.13394","DOIUrl":"https://doi.org/10.1111/jre.13394","url":null,"abstract":"<p><strong>Aim: </strong>To investigate the role of Toll-like receptor 7 (TLR7) in periodontitis and its potential mechanisms.</p><p><strong>Methods: </strong>TLR7 expression in periodontal tissues was analyzed using GEO database single-cell sequencing data and confirmed with gingival samples from healthy individuals and periodontitis patients. In vivo, a mouse model of periodontitis was used to assess the effect of M5049, the TLR7's inhibitor, on alveolar bone loss and inflammation. In vitro, mouse bone marrow-derived macrophages (BMDMs) were treated with Imiquimod to activate TLR7. The inflammatory response was further evaluated using Pg-LPS-stimulated BMDMs, with TLR7 knockdown and NF-κB inhibition by PDTC.</p><p><strong>Results: </strong>TLR7 expression in the gingival tissues of periodontitis patients was significantly elevated compared to healthy gingival tissues. In vivo, TLR7 inhibition reduced bone loss and inflammation, with decreased osteoclast formation and cytokine expression. In vitro, activation of TLR7 heightened inflammation; conversely, TLR7 knockdown and NF-κB inhibition diminished cytokine expression, suggesting a role for NF-κB in TLR7-mediated inflammatory responses.</p><p><strong>Conclusion: </strong>TLR7 is upregulated in periodontitis and may promote the progression of the disease by activating the NF-κB signaling pathway, potentially serving as a therapeutic target. The findings reveal a novel role for TLR7 in periodontitis and highlight the TLR7-NF-κB axis as a key pathway in disease pathogenesis, with broader implications for understanding and treating inflammatory conditions.</p>","PeriodicalId":16715,"journal":{"name":"Journal of periodontal research","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143501992","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}
Qinglian Zhang, Hanxin Que, Shengming Xu, Leyan Xu, Jian Lin, Hui Deng, Ke Deng, Yi Wang
{"title":"The Association of Intake of Vitamin Mixtures With Periodontitis: A Machine Learning Approach on NHANES.","authors":"Qinglian Zhang, Hanxin Que, Shengming Xu, Leyan Xu, Jian Lin, Hui Deng, Ke Deng, Yi Wang","doi":"10.1111/jre.13387","DOIUrl":"https://doi.org/10.1111/jre.13387","url":null,"abstract":"<p><strong>Aims: </strong>Previous studies have focused on the association of single vitamin intake with periodontitis. However, the consumption of vitamins is commonly in the form of mixtures. The relationship between the consumption of multiple vitamins and the prevalence of periodontitis needs to be investigated.</p><p><strong>Methods: </strong>In this cross-sectional study, 8512 participants with full-mouth periodontal examination records and vitamin intake (vitamins A, B<sub>1</sub>, B<sub>2</sub>, B<sub>6</sub>, B<sub>12</sub>, C, D, E, and K) data from the US National Health and Nutrition Examination Survey (NHANES, 2009-2014) datasets were included. GLM and Bayesian kernel machine regression (BKMR) were used to estimate the association of individual and mixed vitamins with periodontitis, respectively. Sensitivity analyses were performed using mean probing depth and mean clinical attachment loss as continuous indicators of periodontitis severity.</p><p><strong>Results: </strong>Vitamins A (OR = 0.90, 95% CI: 0.95-0.99) and E (OR = 0.95, 95% CI: 0.93-0.97) were both negatively associated with periodontitis in GLM estimates and BKMR modeling in the context of vitamin mixtures. Moreover, the intake of vitamin mixtures within a certain range (< 75% percentile) was negatively associated with the estimated risk of periodontitis, which was predominantly driven by vitamins A and E. A potential interaction between vitamins A and E in their association with periodontitis was observed. Similar findings were found in sensitive analyses.</p><p><strong>Conclusions: </strong>BKMR estimates suggested that higher intake of vitamin mixtures might account for decreased odds of periodontitis, with vitamins A and E identified as the most influential factors. Future studies are highly warranted to clarify the underlying mechanisms.</p>","PeriodicalId":16715,"journal":{"name":"Journal of periodontal research","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143483562","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":"Implant Dentistry: The Past, the Present, the Future","authors":"Niklaus P. Lang","doi":"10.1111/jre.13388","DOIUrl":"10.1111/jre.13388","url":null,"abstract":"","PeriodicalId":16715,"journal":{"name":"Journal of periodontal research","volume":"60 2","pages":"97-100"},"PeriodicalIF":3.4,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143468331","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}
Manuel Toledano-Osorio, Carolina Cifuentes-Jiménez, Manuel Toledano, Mariano Sanz, Osorio Raquel
{"title":"Amyloid-β and Bacterial Lipopolysaccharide at Implants With Peri-Implantitis: Ex Vivo Colocalization and Decontamination Protocol.","authors":"Manuel Toledano-Osorio, Carolina Cifuentes-Jiménez, Manuel Toledano, Mariano Sanz, Osorio Raquel","doi":"10.1111/jre.13386","DOIUrl":"https://doi.org/10.1111/jre.13386","url":null,"abstract":"<p><strong>Aim: </strong>To study the differential presence of amyloid-β and bacterial lipopolysaccharide (LPS) in freshly extracted titanium implants, either affected by peri-implantitis (PI) or explanted by other causes, and to address a method for removal LPS and amyloid-β from contaminated surfaces.</p><p><strong>Methods: </strong>Twenty-four explanted implants were harvested from patients with (n = 12) or without (n = 12) peri-implantitis, and their surfaces were analyzed by attenuated total reflectance (ATR) and Fourier transform infrared spectroscopy (FTIR) to localize amyloid-β and LPS. Presence of amyloid-β on the implants surfaces was further analyzed by light microscopy after specific amyloid staining with Congo red. Titanium discs were contaminated with LPS and amyloid-β, these discs as well as six contaminated implants were treated with 0.25% NaOCl to assess its decontamination ability.</p><p><strong>Results: </strong>LPS and amyloid-β were observed at PI affected implant surfaces, but not in implants extracted by other causes. 0.25% NaOCl application was an efficient method for removing LPS and amyloid-β from titanium surfaces.</p><p><strong>Conclusions: </strong>The concurrent presence of LPS and amyloid-β on the surface of implants affected by PI was demonstrated and it may act as potential comediators of PI inflammatory process. Eliminating these products from implants surfaces is possible after a proteolytic agent (0.25% NaOCl) application.</p>","PeriodicalId":16715,"journal":{"name":"Journal of periodontal research","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143440468","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}
Yuwang Li, Fenglan Li, Haitao Liu, Limei Li, Jie Hao
{"title":"Extracellular Vesicles From Dental Pulp Cells Promote Osteogenic Differentiation in Periodontal Ligament Cells.","authors":"Yuwang Li, Fenglan Li, Haitao Liu, Limei Li, Jie Hao","doi":"10.1111/jre.13390","DOIUrl":"https://doi.org/10.1111/jre.13390","url":null,"abstract":"<p><strong>Aim: </strong>Periodontal osseous defects are mainly caused by periodontitis, which seriously affects the quality of patient life. Dental pulp cells (DpCs)-derived extracellular vesicles (EVs) can effectively promote tissue regeneration. Homeobox A9 (HOXA9) mRNA is abundant in EVs derived from DSCs, which may be related to promoting alveolar bone regeneration, but the specific mechanism is unclear. We aimed to elucidate the mechanism through which HOXA9 from DPCs-derived EVs can impact the osteogenic differentiation of periodontal ligament cells (PDLCs).</p><p><strong>Methods: </strong>DPCs-derived EVs were isolated and characterized by transmission electron microscopy (TEM), nanoparticle tracking analysis (NTA), and western blot. Lipopolysaccharide (LPS) was employed to induce the inflammatory environment. Cell viability was assessed by CCK8 assay. Calcium deposition was determined by Alizarin red staining. H3K27ac enrichment in the FLI1 enhancer region and the interaction between C/EBPα, HOXA9, and FLI1 were analyzed by ChIP assay. The interaction between HOXA9 and FLI1 enhancer in 293T cells was analyzed by dual luciferase reporter gene assay.</p><p><strong>Results: </strong>DPCs-derived EVs promoted PDLC osteogenesis under LPS treatment and increased HOXA9 expression in PDLCs. HOXA9 knockdown in DPCs reversed the promoting effect of DPCs-derived EVs on PDLC osteogenic differentiation. HOXA9 from DPCs-derived EVs promoted H3K27ac enrichment in the FLI1 enhancer region by facilitating HOXA9 competitively binding FLI1 enhancer region with C/EBPα. Moreover, HOXA9 from DPCs-derived EVs promoted PDLC osteogenesis by activating the PI3K/AKT pathway through upregulating FLI1.</p><p><strong>Conclusion: </strong>HOXA9 from DPCs-derived EVs promoted PDLC osteogenic differentiation by activating the PI3K/AKT pathway through promoting H3K27ac enrichment in the FLI1 enhancer region and upregulating FLI1. Our study identified a previously unknown mechanism that HOXA9/FLI1 signaling axis participates in the processes of EVs derived from DPCs to treat bone tissue injury. Our research presents a theoretical basis for using EVs derived from DPCs to treat bone tissue injury.</p>","PeriodicalId":16715,"journal":{"name":"Journal of periodontal research","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143365215","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}