Journal of periodontal research最新文献

{"title":"Periodontal Medicine Rewired: Mechanisms Linking Periodontitis to Systemic Diseases.","authors":"Mario Romandini, George Hajishengallis, Mike Curtis, Giacomo Baima","doi":"10.1111/jre.70099","DOIUrl":"https://doi.org/10.1111/jre.70099","url":null,"abstract":"<p><p>Periodontitis is now recognized not merely as a localized oral condition but as a systemic disease linked to over 70 communicable and non-communicable conditions. This Review explores the key mechanistic pathways-or \"gum-shots\"-underpinning the systemic impact of periodontitis. Seven interwoven mechanisms are identified. The first, microbial translocation, involves oral pathobionts and virulence factors breaching anatomical barriers and gaining systemic access via hematological, respiratory, and enteral routes, contributing to tissue damage at extra-oral sites. The second, systemic (meta)inflammation, implicates both the spillover of inflammatory mediators from periodontal tissues into circulation and the immune response to translocated pathogens, fueling pro-inflammatory processes. The third, maladaptive myelopoiesis, involves the periodontitis-associated maladaptive trained immunity and aging-related clonal hematopoiesis of indeterminate potential in the bone marrow, leading to myeloid cells with heightened proinflammatory potential. The fourth, immune players trafficking, centers on the systemic repercussions of periodontally generated autoantibodies, translocated orally primed inflammatory cells, and other local immune events. The fifth, masticatory dysfunction-mediated dietary alterations, involves compromised chewing efficiency that alters dietary intake, resulting in nutritional and metabolic imbalances. The sixth, functional dysregulation of the oral microbiome, describes how periodontitis alters the metabolic activity of this densely populated microbial \"superorganism\", with downstream effects on both oral and systemic physiology. The final mechanism, shared underlying vulnerabilities, refers to background entities-such as biological aging, oxidative stress, psychosocial stress, (epi)genetic predispositions, certain viral infections, and potentially other as-yet-unknown contributors-that drive multi-morbidity, including periodontitis. By dissecting these interconnected pathways, this critical Review challenges the traditional dichotomy of direct versus indirect mechanisms, revealing a more intricate and dynamic interplay.</p>","PeriodicalId":16715,"journal":{"name":"Journal of periodontal research","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-04-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147723152","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":"Periodontitis and Incident Diabetes Mellitus: A Nationwide Cohort Study From Korea.","authors":"Shi Jun Park, Su-Min Park, Eun-Cheol Park","doi":"10.1111/jre.70111","DOIUrl":"https://doi.org/10.1111/jre.70111","url":null,"abstract":"<p><p>This nationwide cohort study demonstrates that treated periodontitis was independently associated with a 33% increased risk of incident diabetes. Using a treatment-based exposure and a washout design, findings emphasize the importance of periodontal care in metabolic disease prevention.</p>","PeriodicalId":16715,"journal":{"name":"Journal of periodontal research","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147699123","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":"","authors":"","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":16715,"journal":{"name":"Journal of periodontal research","volume":"61 3","pages":"225-232"},"PeriodicalIF":3.4,"publicationDate":"2026-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148078599","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":"","authors":"","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":16715,"journal":{"name":"Journal of periodontal research","volume":"61 3","pages":"225-232"},"PeriodicalIF":3.4,"publicationDate":"2026-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148080244","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":"Integrative Human Genomic and Pharmacological Analyses Identify CACNB4 as a Druggable Target for Periodontitis.","authors":"Yixuan Jiang, Zhengyu Guan, Xiu Yao, Xiaomeng Liu, Dan Qiu, Boyuan Sun, Hongjiao Li","doi":"10.1111/jre.70073","DOIUrl":"10.1111/jre.70073","url":null,"abstract":"<p><strong>Aim: </strong>To identify and validate druggable gene targets for periodontitis using integrative human genomic analyses and to explore their therapeutic potential through pharmacological evaluation.</p><p><strong>Methods: </strong>To identify therapeutic targets for periodontitis, we performed Mendelian randomization (MR) and colocalization analyses using the cis-expression quantitative trait loci (cis-eQTL) data of druggable genes and genome-wide association studies (GWAS) data. This approach allowed us to pinpoint druggable gene targets significantly associated with periodontitis, which were then validated by immunohistochemistry and quantitative reverse transcription polymerase chain reaction (qRT-PCR). Next, we applied drug prediction and molecular docking to identify candidate drugs for the key druggable target. Finally, pharmacological analyses were conducted to evaluate the efficacy of these drugs in vitro and in vivo.</p><p><strong>Results: </strong>A total of six genes (CACNB4, PSMA4, GAA, FGF2, AURKAIP1, and ADAM12) were found to be causally associated with periodontitis in the MR analysis, of which two (CACNB4 and PSMA4) were further supported by colocalization analyses. CACNB4 was significant in both cohorts in MR analysis and supported by localization and experimental evidence. Moreover, the reliability of this target was confirmed in patient samples. We then identified drugs with repurposing potential that target CACNB4, namely verapamil and safinamide. Pharmacological analyses showed that both agents attenuated osteoclast differentiation, indicating therapeutic potential. Importantly, validation at the cellular level confirmed the activity of these candidate drug targets.</p><p><strong>Conclusion: </strong>Through MR analysis, we identified CACNB4 as a potential druggable gene for periodontitis. Among the drugs targeting CACNB4, verapamil and safinamide emerged as the most promising candidates for periodontitis treatment. Pharmacological studies further demonstrated that these agents may inhibit osteoclast differentiation by targeting CACNB4, thereby offering potential therapeutic options for periodontitis.</p>","PeriodicalId":16715,"journal":{"name":"Journal of periodontal research","volume":" ","pages":"396-405"},"PeriodicalIF":5.4,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145911802","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":"Soft Tissue Augmentation Around Dental Implants: Techniques, Timing, and Comparative Efficacy-A Systematic Review and Network Meta-Analysis.","authors":"Enrico Cafasso, Giacomo Baima, Alessandro Campagna, Lorenzo Tavelli, Mario Aimetti","doi":"10.1111/jre.70100","DOIUrl":"10.1111/jre.70100","url":null,"abstract":"<p><strong>Aim: </strong>The peri-implant soft tissue phenotype, including keratinized tissue width (KTW) and mucosal thickness (MT), plays a pivotal role in maintaining peri-implant health and stability. Various soft tissue augmentation (STA) procedures have been developed to enhance these components, employing different grafting techniques and materials. The aim of the present systematic review is to compare the effectiveness of different techniques as well as different surgical timing in order to establish their relative efficacy.</p><p><strong>Methods: </strong>A systematic review and Bayesian network meta-analysis (NMA) was conducted following PRISMA-NMA guidelines. Randomized controlled trials (RCTs) evaluating STA around dental implants were included, focusing on KTW and MT gain as primary outcomes. Pairwise and indirect comparisons were performed using a hierarchical Bayesian model with Markov chain Monte Carlo simulations. Treatment effects were expressed as mean differences (MD) with 95% credible intervals. Additionally, subgroup analyses explored apically positioned flap (APF)-based and bilaminar techniques separately, while meta-regression assessed the influence of surgical timing.</p><p><strong>Results: </strong>A total of 48 RCTs were included in the qualitative analysis, and 46 in the NMA. For KTW gain, APF + free gingival graft (FGG) was the most effective treatment [range of MD: 0.22-4.11 mm], whereas APF alone showed limited efficacy compared to no intervention. Bilaminar techniques did not result in significant KTW gain. For MT gain, bilaminar techniques showed the best results, with connective tissue graft (CTG) displaying the best performance [range of MD: 0.02 to 0.94 mm], followed by xenogeneic collagen matrix and buccally displaced flap. Timing did not significantly influence MT gain, while \"delayed time points\" might positively influence KTW. Longitudinal analysis showed variability in stability across treatments, with APF + FGG and CTG maintaining higher performance over time.</p><p><strong>Conclusion: </strong>APF + FGG is the most reliable approach for increasing KTW, while CTG remains the gold standard for MT enhancement. The choice of technique and graft material appears more critical than surgical timing. Long-term stability of tissue dimensions and standardization of reporting across future trials are essential to refine clinical decision-making in STA procedures.</p>","PeriodicalId":16715,"journal":{"name":"Journal of periodontal research","volume":" ","pages":"332-354"},"PeriodicalIF":3.4,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147486314","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":"Matrix Metalloproteinases in Periodontal and Peri-Implant Diseases: Contribution to Their Pathogenesis, Diagnosis, and Treatment.","authors":"Timo Sorsa, Lorne M Golub, Julie Toby Thomas, Pietro Leone, Sukumaran Anil, Veli-Jukka Uitto","doi":"10.1111/jre.70062","DOIUrl":"10.1111/jre.70062","url":null,"abstract":"<p><p>Matrix metalloproteinases (MMPs) represent a family of 23 zinc-dependent endopeptidases central to extracellular matrix remodeling in periodontal and peri-implant diseases. This comprehensive review examines the pathogenic mechanisms, diagnostic applications, and therapeutic targeting potential of the entire MMP family in periodontitis and peri-implantitis. All MMP subfamilies, collagenases (MMP-1, -8, -13), gelatinases (MMP-2, -9), stromelysins (MMP-3, -10, -11), matrilysins (MMP-7, -26), membrane-type MMPs (MT1-6), and others, demonstrate distinct expression patterns and substrate specificities in diseased tissues. MMP-8 and MMP-9 emerge as primary biomarkers, showing 5-6-fold elevations in active periodontitis compared to health, with corresponding increases in activation ratios and decreases in tissue inhibitor of metalloproteinase (TIMP) levels. Diagnostic applications reveal point-of-care active MMP-8 (aMMP-8) immunotests achieve 70%-85% sensitivity and 65%-80% specificity for periodontitis detection, though standardization challenges limit clinical implementation. Salivary and gingival crevicular fluid MMP profiling demonstrates disease-specific signatures, with MMP-8/TIMP-1 ratios serving as progression indicators. Therapeutically, MMP modulation strategies include FDA-approved subantimicrobial dose doxycycline (SDD), which achieves a 40%-60% reduction in clinical attachment loss. Novel approaches encompass selective MMP inhibitors, pro-resolving mediators, and host-modulation therapies, with emerging AI-assisted personalized treatment protocols showing promise. Critically, peri-implantitis exhibits more severe MMP dysregulation than periodontitis, with MMP: TIMP ratios reaching 50:1 versus 20:1, accelerated bone loss patterns, and distinct MT-MMP involvement reflecting titanium surface interactions. Translation barriers include the need for biomarker standardization, the complexity of MMP redundancy, and the requirement for personalized diagnostic thresholds. Future directions emphasize integrating MMP signatures with multi-omics approaches, developing selective inhibitors, and establishing evidence-based clinical guidelines for MMP-targeted precision periodontal medicine.</p>","PeriodicalId":16715,"journal":{"name":"Journal of periodontal research","volume":" ","pages":"355-371"},"PeriodicalIF":3.4,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146010873","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":"Extracellular Vesicles in Gingival Crevicular Fluid as Indicators of Periodontitis and Early Response to Non-surgical Periodontal Therapy.","authors":"Pingping Han, Andrew Liaw, Akila Suboda Vithanage, Carlos Salomon, Sašo Ivanovski","doi":"10.1111/jre.70070","DOIUrl":"10.1111/jre.70070","url":null,"abstract":"<p><p>Our study aims to profile EV subtypes and cytokines (IL-4, IL-10, IL-1β, TNF-α) across (1) shallow pockets (≤ 3 mm) in healthy, gingivitis, and periodontitis patients, and (2) deep pockets (≥ 6 mm) in periodontitis patients before and 1 month after NSPT. Preliminary data suggest that sEV-IL-4 and CD9⁺ sEV may reflect treatment response in periodontitis, being elevated in responding versus nonresponding sites.</p>","PeriodicalId":16715,"journal":{"name":"Journal of periodontal research","volume":" ","pages":"421-423"},"PeriodicalIF":5.4,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146010557","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":"SIGIRR Inhibits Periodontitis-Associated Inflammation and Promotes Regeneration by Blocking Sp1 Nuclear Translocation.","authors":"Xuanxuan Yang, Weixu Li, Lizi Jin, Zhixiang Li, Bolun Zhang, Kaijin Hu, Meng Cao","doi":"10.1111/jre.70074","DOIUrl":"10.1111/jre.70074","url":null,"abstract":"<p><strong>Aim: </strong>To investigate the contribution of the Single Immunoglobulin Interleukin-1 Receptor-Related Molecule (SIGIRR), a recently described negative mediator of inflammation signaling, in experimental periodontitis pathogenesis.</p><p><strong>Methods: </strong>A comprehensive approach was employed, including the analysis of human periodontal tissues, in vitro experiments with Periodontal ligament stem cells (PDLSCs), and validation in a rat experimental periodontitis model. The mechanistic link between LPS stimulation and SIGIRR downregulation was investigated, focusing on the p38 pathway and transcription factor Sp1. Functional effects of SIGIRR overexpression on inflammatory cytokine production were assessed.</p><p><strong>Results: </strong>SIGIRR expression was markedly downregulated in periodontitis and LPS-stimulated PDLSCs. This downregulation was mechanistically linked to LPS activation of the p38 pathway, which impaired nuclear translocation of the transcription factor Sp1, a key positive regulator of SIGIRR transcription. SIGIRR overexpression in PDLSCs significantly attenuated LPS-induced production of pro-inflammatory cytokines (IL-6, IL-8, TNF-α). Local administration of a SIGIRR-overexpressing lentivirus in the rat experimental periodontitis model effectively reduced local pro-inflammatory cytokine levels, and promoted alveolar bone repair.</p><p><strong>Conclusion: </strong>Together, our findings establish a unique role for p38-Sp1-SIGIRR axis in the pathogenesis of experimental periodontitis and provide evidence that SIGIRR gene therapy promises to offer an alternative option for inflammation blockade and bone repair, facilitating the development of a novel therapeutic strategy.</p>","PeriodicalId":16715,"journal":{"name":"Journal of periodontal research","volume":" ","pages":"406-417"},"PeriodicalIF":5.4,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145997701","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":"Soft-Tissue Phenotype Modification as an Adjunct to the Treatment of Peri-Implant Mucositis-A Quasi-Randomized Clinical Trial.","authors":"Zeynep Aksu, Sila Cagri Isler, Berrin Unsal, Andrea Roccuzzo, Mario Romandini","doi":"10.1111/jre.70014","DOIUrl":"10.1111/jre.70014","url":null,"abstract":"<p><strong>Aim: </strong>This quasi-randomized clinical trial evaluated the additional benefit of soft-tissue phenotype modification via free palatal graft (FPG) as an adjunct to non-surgical therapy for peri-implant mucositis. A secondary objective was to determine whether any observed effects were mediated by improved plaque control.</p><p><strong>Methods: </strong>Forty-three patients (55 implants) with peri-implant mucositis and keratinized tissue width (KTW) < 2 mm were enrolled. One month after oral hygiene instructions and non-surgical treatment, participants were quasi-randomly allocated to either an FPG procedure (test group, n = 22) or no additional intervention (control group, n = 21). The primary outcome was bleeding on probing (BoP) extent at 6 months (i.e., number of bleeding sites per implant). Secondary outcomes included peri-implant phenotype parameters (KTW, tissue thickness, and vestibular depth), plaque extent, and other peri-implant health measures (BoP severity, probing pocket depth [PPD], peri-implant soft-tissue dehiscence [PISTD], and treatment success). Intergroup comparisons were performed using regression analyses, and a mediation analysis assessed whether treatment effects were mediated by improved plaque control.</p><p><strong>Results: </strong>At 6 months, FPG significantly increased KTW (mean difference [MD] = 2.36 mm; p < 0.001) and tissue thickness (MD = 0.97 mm; p < 0.001), while reducing plaque extent (MD = -1.49; p < 0.001), compared with the control group. BoP extent was significantly lower in the test group (0.75 ± 1.07) than in controls (1.83 ± 1.20) (MD = -1.06; 95% CI: -1.67 to -0.44; p = 0.001). Additionally, the test group exhibited lower BoP severity (MD = -0.50; p < 0.001) and higher treatment success (OR = 8.44; p = 0.001). No significant differences were observed in PPD and PISTD. Mediation analysis suggested that the observed benefits of FPG on peri-implant health were largely independent of improved plaque control.</p><p><strong>Conclusion: </strong>FPG effectively modified the peri-implant soft-tissue phenotype and, as an adjunct to non-surgical therapy, provided additional benefits in managing peri-implant mucositis. The effects on peri-implant health were not attributable to improved plaque control.</p>","PeriodicalId":16715,"journal":{"name":"Journal of periodontal research","volume":" ","pages":"372-381"},"PeriodicalIF":3.4,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144731901","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}