Journal of periodontal research最新文献

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.

Periodontal and craniofacial tissue defects are complex regenerative targets as the reconstitution of tissue heterogeneity, interconnection and function is essential for favorable clinical outcomes. Periodontal tissues are additionally challenged by the bacterial and immunological factors associated with oral regeneration. Hydrogels are extracellular matrix-like hydrated polymer networks that represent a diverse class of regenerative materials. Current applications of hydrogels for periodontal and craniofacial tissue regeneration include either independent or combined approaches including serving as scaffolds to support cell migration, proliferation, differentiation and matrix deposition at the defective site, and/or the delivery of biomolecular therapies. The aim of this review is to highlight and classify the hydrogel strategies currently used in the clinical area for the regeneration of periodontal and craniofacial tissues. In addition, we provide a perspective on emerging hydrogel technologies and regenerative strategies under development that may be utilized to address unmet clinical needs.

Periodontitis is a chronic, host-mediated inflammatory disease in which microbial dysbiosis and dysregulated immune responses drive the destruction of tooth-supporting tissues. Although conventional therapy remains centered on mechanical biofilm control, persistent inflammation and alveolar bone loss in susceptible individuals underscore the need for adjunctive strategies. Translating preclinical discoveries into predictable clinical outcomes, however, remains a major challenge in periodontal research. This narrative review integrates two interrelated themes, translational research methodology and adjunctive therapeutic innovation, to critically examine how preclinical findings can be more effectively bridged to clinical practice in periodontitis management. Evidence was synthesized from experimental, translational, and clinical studies retrieved from PubMed, Scopus, and Web of Science up to September 2025. Emphasis was placed on mechanistic insights, model validity, and translational feasibility across host-modulatory, natural, probiotic, and device-based adjuncts. Animal models remain indispensable for mechanistic understanding and therapeutic testing but face biological and methodological limitations that hinder direct extrapolation to humans. Interspecies differences, short disease kinetics, and non-standardized endpoints constrain translational predictability. Addressing these gaps requires refined modeling, standardized outcomes, and integration of systemic risk factors. Within this methodological framework, several adjunctive modalities, including specialized pro-resolving mediators, probiotics, natural compounds such as curcumin and resveratrol, and device-based therapies like antimicrobial photodynamic therapy demonstrate promising anti-inflammatory, osteoimmunomodulatory, and regenerative effects. Emerging translational tools such as bioresponsive drug delivery systems, nanocarriers, 3D-printed scaffolds, and AI-driven precision periodontics may further enhance clinical relevance and patient-specific targeting. Advancing adjunctive periodontal therapy demands harmonized translational models, bioresponsive delivery platforms, and precision diagnostic tools that bridge preclinical efficacy with real-world outcomes. By aligning methodological rigor with therapeutic innovation, translational research can accelerate the safe and effective clinical integration of next-generation adjunctive treatments in periodontitis.

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.

Aim: 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.

Methods: 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.

Results: 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.

Conclusion: 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.

Aim: To identify and validate druggable gene targets for periodontitis using integrative human genomic analyses and to explore their therapeutic potential through pharmacological evaluation.

Methods: 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.

Results: 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.

Conclusion: 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.

Cross-sectional studies capture health states, exposures, and risk factors at a single time point, providing essential data for estimating disease prevalence and informing public health planning. These studies serve multiple epidemiological purposes: characterizing population health, monitoring temporal trends through repeated surveys, and evaluating interventions via interrupted time series designs. They also offer practical advantages for validating self-reported measures and creating diagnostic models. Cross-sectional designs are efficient and well-suited to descriptive epidemiology, but they have limited utility for causal inference. The simultaneous measurement of exposures and outcomes creates temporal ambiguity that fundamentally constrains etiologic interpretation. However, causal inferences can be strengthened under specific conditions-when temporal sequence is unambiguous (e.g., genetic variants preceding outcomes) or when valid instrumental variables are available. This methodological tutorial equips readers with concepts and tools to critically appraise cross-sectional studies across the application domains outlined and to design and analyze their own cross-sectional studies that yield high-quality epidemiologic descriptions.

Soft tissue augmentation around teeth and dental implants is a central aspect of periodontal and peri-implant plastic surgery. Autogenous soft tissue grafts are generally regarded as the gold standard for increasing keratinized mucosa, mucosal thickness, and soft tissue height, supported by extensive long-term evidence. However, limitations such as restricted tissue availability, increased surgical time, and donor-site morbidity have encouraged the development of soft tissue graft substitutes, including xenogeneic and allogeneic matrices, and collagen derivatives, among other biomaterials. Over the past two decades, these alternatives have shown promising results, particularly in sites with favorable anatomical conditions, including optimal bone support, tall and wide papillae, and adequate hard and soft tissue phenotype; although their predictability remains variable across the literature and is often lower than that of autogenous grafts in complex defects and esthetically demanding areas. Nevertheless, the growing emphasis on patient-reported outcomes has led several authors to explore the use of graft substitutes in different clinical scenarios, sometimes in combination with smaller autogenous grafts. This manuscript aims to summarize the current state-of-the-art on soft tissue graft substitutes for managing deficiencies at both teeth and implant sites. A comprehensive literature review is provided, together with clinical decision trees designed to guide clinicians in selecting autogenous grafts versus substitutes across different scenarios. These tools highlight the main factors influencing treatment selection, including baseline keratinized mucosa, buccal bone conditions, site anatomy, esthetic requirements, and patient preference. By integrating current evidence with practical algorithms, this review seeks to support clinicians in making informed, patient-centered decisions regarding soft tissue augmentation at teeth and implants.