Journal of periodontal research最新文献

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.

Aims: To investigate how Porphyromonas gingivalis induces endothelial dysfunction, focusing on the regulatory role of Sirtuin 3 (Sirt3) in mitochondrial function.

Methods: Differentially expressed Sirtuin family genes in P. gingivalis-infected human aortic endothelial cells (HAECs) were identified through RNA sequencing and validated by quantitative real-time PCR and Western blot. Mitochondrial and endothelial functions were assessed in P. gingivalis-infected HAECs with or without Sirt3-specific agonist Honokiol. Cyclophilin D (CypD) K167 point mutation plasmids were constructed, and Co-immunoprecipitation was performed to investigate the Sirt3-CypD interaction. The vasorelaxation of aortas from mice orally administrated with P. gingivalis was also evaluated.

Results: Porphyromonas gingivalis infection in HAECs resulted in mitochondrial and endothelial dysfunction. Mechanistic studies revealed that Sirt3-mediated deacetylation of CypD at K167 was pivotal in alleviating P. gingivalis-induced mitochondrial and endothelial dysfunction. Oral inoculation of P. gingivalis in mice significantly impaired endothelial-dependent vasodilation, disrupted aortic endothelial integrity, increased endothelial cell apoptosis, and elevated mitochondrial reactive oxygen species production. Notably, Sirt3 activation reversed mitochondrial and endothelial dysfunction induced by P. gingivalis both in vivo and in vitro.

Conclusion: The present study demonstrated that P. gingivalis induced mitochondrial and endothelial dysfunction, which was mediated through Sirt3-dependent CypD deacetylation.

Aim: The study aimed to elucidate a putative association between severe periodontitis and the incidence of recurrent cardiovascular events in patients with cardiovascular disease (CVD) within 10 years after their initial hospitalisation.

Methods: A cohort of 1002 stationary patients with angiographically proven CVD was included. They were examined regarding prevalence of severe periodontitis (≥ 30% of the teeth with proximal attachment loss of ≥ 5 mm), probing depth, clinical attachment loss, bleeding on probing, number of missing teeth and oral care habits. Recurrent events were summarised as combined end point (myocardial infarction, stroke/transitory ischemic attack, cardiovascular death and death caused by stroke). Survival analyses were carried out after a 10-year follow-up period. Hazard ratios (HRs) were adjusted for known cardiac risk factors using Cox regression.

Results: The follow-up was completed by 792 patients. The overall incidence of the combined end point was 42.8%. Severe periodontitis was associated with recurrent cardiovascular events (adjusted hazard ratio [HR] = 1.26, 95% confidence interval [CI] 1.0-1.58 and Standard error [SE] 0.11), whereas both, tooth brushing more than once a day (adjusted HR = 0.74, 95% CI 0.57-0.97, SE 0.13) and performing interdental hygiene (adjusted HR = 0.71, 95% CI 0.52-0.99, SE 0.16) decreased this risk.

Conclusions: Severe periodontitis is a putative risk factor for recurrent cardiovascular events.

Trial registration: ClinicalTrials.gov identifier: NCT01045070.

Aims: Elevated levels of Herpes Simplex Virus 1 (HSV-1) have been reported in periodontitis, however, the tropism and relationship with periodontal inflammation are poorly characterized. This study investigated how inflammation affects viral tropism toward human periodontal ligament stem cells (hPDLSCs).

Methods: HSV-1 gB and gD transcripts in healthy and diseased human gingiva were measured by RT-qPCR and confirmed in HSV-1-infected murine gingiva. HSV-1 infection in hPDLSCs was analyzed by imaging and flow cytometry. hPDLSCs were individually treated with IL-6, TNF-α, GMCSF, IL-10, or PgLPS, and HSV-1 replication was assessed by infecting with the 17 GFP strain. Lineage markers in virally infected hPDLSCs during osteogenic differentiation were measured by RT-qPCR and immunofluorescence in vitro and validated in vivo. Mice subjected to ligature-induced periodontitis (LIP) and infected with HSV-1 were examined for gingival histology, inflammatory cytokines, and alveolar bone loss.

Results: Inflamed human gingiva showed higher expression of viral transcripts compared to healthy controls. In mouse oral HSV-1 infection, gB and gD expression increased over time, with higher levels in mice with ligature-induced periodontitis. Virus infected hPDLSCs challenged with inflammatory mediators or PgLPS showed higher GFP, while IL-10 treatment attenuated GFP levels. Importantly, HSV-1 17 GFP infection affected osteoblast lineage commitment by promoting the expression of key transcription factors in vitro and in vivo. Compared to the LIP alone group, higher levels of inflammatory markers and bone loss were evident in HSV-1 infected with LIP.

Conclusion: hPDLSCs are trophic to HSV-1 in vitro and in vivo, with periodontal inflammation playing a significant role in viral tropism.

Aims: Diabetes induces disorders in macrophage immunometabolism, leading to increased destruction of periodontal tissue. Identifying key factors to restore metabolic alterations and promote resolution of inflammation remains an unmet objective.

Methods: In the present study, the effect of macrophage efferocytosis on inflammatory regression and tissue repair was assessed using a diabetic periodontitis (DPD) model. The mitochondrial function of macrophages cultured under different conditions was assessed in vitro, and macrophage efferocytosis function and polarization phenotypes were examined. Osteogenic differentiation and migration capacity were examined using periodontal ligament stem cells (PDLSCs) co-cultured with macrophages to assess the effect on tissue repair.

Results: We demonstrated that the high-glucose inflammatory microenvironment exacerbated the pro-inflammatory metabolic profile of macrophages and disrupted mitochondrial dynamics. Rats with DPD exhibited heightened periodontal tissue damage during the ligation period, characterized by increased neutrophil infiltration and apoptotic cells. Following ligature removal, the transition to the repair phase was inhibited. Impaired efferocytosis in macrophages led to reduced expression of anti-inflammatory cytokines. Inhibiting excessive mitochondrial division mitigated macrophage damage, ultimately improving the osteogenic differentiation and migration of PDLSCs.

Conclusions: This research suggested the critical role of mitochondria in the resolution of inflammation in diabetic periodontitis through regulating macrophage efferocytosis and interaction with PDLSCs.