Journal of periodontal research最新文献

Aim: Porphyromonas gingivalis lipopolysaccharide (PgLPS) is a significant virulence factor and a driver of early innate immune responses in epithelial cells. The presence of PgLPS in immediate proximity to gingival epithelium induces significant inflammatory responses. In primary human gingival keratinocytes (HGK), we utilized transcriptome analysis to elucidate the change in early gene expression induced by PgLPS.

Methods: HGK cell cultures were treated with PgLPS (4 h), and RNA was extracted and prepared for RNA sequence (RNAseq) analysis. Differentially expressed genes (DEGs) were identified, and potential interactions between these genes were subsequently examined using gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analytic approaches to identify significantly enriched pathways. Expression of genes associated with relevant pathways was evaluated using real-time quantitative reverse-transcription polymerase chain reaction (RT-qPCR).

Results: RNAseq analysis identified 25 DEGs, and GO and KEGG analytic approaches showed related genes expressed in two general pathways. First, pathways broadly related to urokinase and coagulation included the genes PLAU, PLAUR, and SerpinB2. In RT-qPCR analysis, these genes were induced by PgLPS over time (4-24 h), and these data were consistent with PgLPS induction of cell migration. Second, interleukin-1 (IL-1) receptor binding and cytokine-activity pathways were also enriched. Genes associated with these pathways included IL36G, IL1B, IL1RN, and CXCL14. RT-qPCR analysis confirmed PgLPS induction of genes associated with the IL-1family. When expression of IL1B and IL36G genes was examined in relation to their respective antagonists, only IL36G gene expression was increased. CXCL14 gene expression was reduced over time, and this was consistent with RNAseq analysis.

Conclusions: Genes associated with significantly enriched GO and KEGG pathways are relevant to aspects of periodontal disease (PDD) pathogenesis. First, PgLPS induced expression of PLAU, PLAUR, and SerpinB2, and these changes were consistent with an increase in cell migration that was found. Second, both IL36G and IL1B gene expression was significantly induced, but only IL36G in relation to its selective antagonist (IL36RN) was increased. These data support that early upregulation of IL36G may serve as an alarmin that can drive early innate immune inflammatory responses in HGK. Further in vivo testing of these findings is ongoing.

Aims: Orthodontic force (OF) induces a variety of reactions in the periodontal ligament (PDL) that could potentially account for individual variability regarding orthodontic tooth movement (OTM). This study investigates the transcriptomic profile of human PDL tissue subjected to OF in vivo for 7 and 28 days, additionally comparing the differences between maxillary and mandibular PDL.

Methods: Healthy patients requiring orthodontic premolar extractions were randomly assigned to one of three groups: control (CG) where no OF was applied, 7 days and 28 days, where premolars were extracted either 7 or 28 days after the application of a 50-100 g OF. Total RNA was extracted from the PDL tissue and analyzed via RNA-seq. Differentially expressed genes (DEGs) were identified using a false discovery rate and fold change threshold of < 0.05 and ≥ 1.5 respectively. Functional and Protein-Protein Interaction analysis were performed.

Results: After 7 days of OF, the reaction of PDL to OF is characterized by cell responses to stress, increased bone resorption, inflammation and immune response, and decreased bone formation. In contrast, after 28 days, bone regeneration is more prominent, and processes of bone homeostasis, immune response, and cell migration are present. The response of maxillary and mandibular PDL was different. Bone resorption was observed in the maxilla at 7 and 28 days, while in the mandible expression of cell proliferation and transcriptional activity were predominant after 28 days of OF.

Conclusions: The early reaction of the PDL to OF corresponds with increased bone resorption and decreased bone formation. After 28 days, bone formation became more prominent. The maxillary and mandibular PDL present asynchronous responses during OTM. These findings enhance our comprehension of the mechanisms underlying the origin-specific responses of PDL to different lengths of OF, which is potentially relevant in the development of personalized therapeutic strategies.

Flowchart and timeline (in hours) of the in vitro experimental procedures.

Aim: This study investigated the activity and mechanism of action of the iron tetracarboxyphthalocyanine (FeTcPc) on tumor necrosis factor alpha (TNF-α) production and its impact on experimental periodontitis.

Methods: RAW 264.7 macrophages were treated with FeTcPc, activated with lipopolysaccharide (LPS) at 10 ng/mL, and the TNF-α levels were measured, as well as the nuclear factor kappa B (NF-κB) activation. Subsequently, a mouth gel containing 1% FeTcPc was topically administered to the gingival tissue of mice with periodontitis-induced ligatures. Bone loss and the gene expression of Tnfα, p65 (NF-κB), and receptor-activating nuclear factor kappa B ligand (Rankl) were quantified in gingival tissue. Finally, the systemic toxicity of FeTcPc was estimated in Galleria mellonella larvae.

Results: In an activated RAW 264.7 macrophage culture, 100 μM FeTcPc reduced TNF-α release and NF-κB activation. Regarding experimental periodontitis, topical application of mouth gel containing 1% FeTcPc blocked alveolar bone loss. Additionally, 1% FeTcPc reduced the expression of Tnfα, p65 (NF-κB), and Rankl in gingival tissue. Finally, administration FeTcPc at doses ranging from 1 to 1000 mg/kg did not cause acute systemic toxicity in G. mellonella.

Conclusion: Overall, we demonstrated the potential of mouth gel containing FeTcPc as a therapeutic strategy for managing osteolytic inflammatory disorders, such as periodontitis.

Aims: Periodontitis is a prevalent inflammatory disorder affecting the oral cavity, driven by dysbiotic oral biofilm and host immune response interactions. While the major clinical focus of periodontitis treatment is currently controlling oral biofilm, understanding the immune response is crucial to prevent disease progression. Soluble epoxide hydrolase (sEH) inhibition has shown promise in preventing alveolar bone resorption. Triggering receptors expressed on myeloid cells (TREMs) play pivotal roles in regulating inflammation and bone homeostasis, and dysregulation of TREM signaling is implicated in periodontitis. Here, we investigated the impact of sEH inhibition on TREM 1 and 2 expression, associated with inflammatory cytokines, and histologically assessed the inflammatory infiltrate in periodontal tissue.

Methods: The experimental periodontitis model was induced by placing a ligature around the upper second molar. For 14 days, animals were treated daily with a sEH inhibitor (TPPU) or vehicle. The alveolar bone loss was examined using a methylene blue stain. Gingival tissues were used to measure the mRNA expression of TREM-1, TREM-2, IKKβ, NF-κB, IL-1β, IL-6, IL-8, and TNF-α by RT-qPCR. Another set of experiments was performed to determine the histological inflammatory scores.

Results: In a ligature-induced periodontitis model, sEH inhibition prevented alveolar bone loss and reduced TREM1 expression, albeit with a slight elevation compared to the disease-free group. In contrast, TREM2 expression remained elevated, suggesting sustained immunomodulation favoring resolution. The inhibition of sEH reduced the expression of NF-κB, IL-1β, and TNF-α, while no differences were found in the expression of IL-6, IL-8, and IKKβ. In histological analysis, sEH inhibition reduced the inflammatory leukocyte infiltrate in periodontal tissues close to the ligature.

Conclusion: These findings underscore the potential of sEH inhibition to modulate periodontal inflammation by regulating TREM-1 alongside decreased IL-1β and TNF-α expression, highlighting a promising therapeutic approach for periodontitis management.

The aim of the present systematic review of the literature and meta-analysis was to evaluate the efficacy of different protocols of NSPT without any adjunctive therapy in subjects with type 2 diabetes, by considering clinical and patient-centered outcomes. For the purposes of the study randomized controlled clinical trials with more than 3-month follow-up were searched in MEDLINE, EMBASE, and Cochrane Central. Then the articles were screened for inclusion and considered based on the protocols adopted, the outcome measure, follow-up, and the level of glycemic control. A total of 23 articles about 22 studies were included. NSPT was more effective than just oral hygiene measures/no treatment in reducing periodontal probing depth (PPD) and clinical attachment loss (CAL) at 3 months (0.47 mm [0.29-0.65 mm] and 0.50 mm [0.24-0.76 mm], respectively) and 6 months (0.56 mm [0.28-0.84 mm] and 0.45 mm [0.13-0.77 mm], respectively for PPD and CAL) follow-up (very low and low level of evidence). The meta-analysis found no evidence of a difference between full-mouth disinfection versus quadrant protocol clinical outcomes (very low level of evidence). One study found no evidence of a difference in periodontal clinical response between good versus poor glycemic control. Based on the results of the present research NSPT protocols could be considered more efficacious than others in terms of clinical outcomes in subjects with type 2 diabetes. Moreover, NSPT resulted in efficacious improvement of periodontal parameters and HbA1c levels compared to no treatment or oral hygiene instructions alone.

Aim: Periodontitis and peri-implantitis are chronic inflammatory diseases characterized by the destruction of supporting tissues. Despite some similarities, it is essential to understand the differences in how these diseases elicit unique host responses within the oral tissues, including the production of selected matrix metalloproteinases (MMPs) and inflammatory mediators involved in tissue remodelling. The aim of this study was to evaluate the levels of proteolytic enzymes MMP-1, MMP-2, MMP-3, as well as the inflammatory mediators osteopontin (OPN), pentraxin-3 (PTX3), and thymic stromal lymphopoietin (TSLP) in crevicular fluid samples collected from healthy, periodontitis-affected, and peri-implantitis sites.

Methods: Gingival crevicular fluid (GCF) and peri-implant crevicular fluid (PICF) samples were collected from healthy and diseased teeth and implant sites of 163 patients. The MMP-1, MMP-2, MMP-3, OPN, PTX3, and TSLP levels were determined using commercially available immunoassays. A linear mixed model procedure was adopted for multilevel analyses, using biomarker levels as the outcome variable to compare two types of sites. The diagnostic accuracy of the biomarkers was evaluated by Youden's index to estimate the sensitivity, specificity and the area under curve (AUC).

Results: The levels of MMP-1, MMP-2, MMP-3, OPN, and TSLP were higher at sites with periodontitis and peri-implantitis compared to the levels at sites with healthy teeth and healthy implants. No significant differences were observed in the levels of the measured markers between the sites diagnosed with periodontitis and those diagnosed with peri-implantitis. The highest diagnostic potential at implant sites was found for MMP-2 (AUC = 0.74) and TSLP (AUC = 0.72). The highest AUC (0.82) at tooth sites was found for OPN.

Conclusions: The findings indicate that the proteolytic enzyme MMP-2 and the cytokine TSLP might be potential biomarkers for both periodontitis and peri-implantitis, whereas the proinflammatory cytokine OPN may serve as a biomarker for periodontitis. Further studies are required to confirm the utility of these biomarkers and explore their potential clinical applications.

Aim: The high glucose (HG) environment in diabetic periodontitis aggravates the damage of periodontal tissue. Pyroptosis has been shown to be positively correlated with the severity of periodontitis, including macrophage pyroptosis. O-GlcNAcylation is a posttranslational modification that is involved in the pathogenesis of periodontitis. However, whether HG regulates macrophage pyroptosis through O-GlcNAcylation remains uncertain. This study aimed to investigate the effect of HG on the O-GlcNAcylation level of a pyroptosis regulator GSDME in macrophages to further probe the mechanisms of diabetic periodontitis.

Methods: Blood samples were collected from patients with diabetic periodontitis. THP-1 monocytes were induced to differentiate into macrophages by phorbol 12-myristate 13-acetate and then treated with HG to simulate periodontitis in vitro. GSDME expression of blood samples and macrophages was measured by quantitative real-time PCR. Pyroptosis was assessed by propidium iodide staining, measurement of cell viability, cytotoxicity, protein levels of inflammation factors, and pyroptosis-related proteins. O-GlcNAcylation of GSDME was analyzed using co-immunoprecipitation (co-IP), IP, and western blot.

Results: The results showed that GSDME expression was elevated in patients with periodontitis and HG-treated macrophages. HG inhibited cell viability but increased LDH content, levels of IL-1β, IL-18, TNF-α, NLRP3, GSDMD, and Caspase-1, indicating that HG promoted pyroptosis of macrophages, which was reversed by GSDME knockdown. HG treatment increased O-GlcNAcylation in macrophages. Mechanically, GSDME interacted with OGT, and OGT knockdown suppressed O-GlcNAcylation of GSDME at Ser (S)339 site. Knockdown of OGT inhibited pyroptosis in HG-treated macrophages, while GSDME overexpression partially reversed this inhibition.

Conclusion: HG treatment enhanced OGT-mediated GSDME O-GlcNAcylation, thereby augmenting pyroptosis in LPS-induced macrophages. These results may provide a novel sight for the treatment of periodontitis.

Aims: This study aimed to assess the variability and treatment effect heterogeneity in response to non-surgical periodontal therapy (NSPT).

Methods: Data from randomized controlled trials included in two recent systematic reviews on the effect of NSPT on mean clinical attachment loss (CAL), mean probing pocket depth (PPD), percentage of sites with bleeding on probing (%BOP), PPD ≤3 mm (%PD ≤3 mm), and C-reactive protein levels (CRP) at 3-12-month follow-up among adults with systemic diseases or conditions were used. In these trials, the control arms received no treatment, hygiene advice, or supragingival scaling. The Bayesian meta-regression models were utilized to assess the variability ratios between NSPT and control groups.

Results: Data from 36 trials on mean PPD, 32 trials on mean CAL, eight trials on %PD ≤3 mm, 31 trials on %BOP and 19 trials on CRP were used. Variability in mean CAL and CRP was approximately 10% higher in the NSPT arms than in the control arms, hinting that there may be room for treatment effect heterogeneity. Instead, variability in mean PPD, %BOP, and %PD ≤3 mm was lower in the NSPT arms than in the control arms.

Conclusion: Potential treatment effect heterogeneity in response to NSPT was observed for CRP and mean CAL. However, substantial measurement error in CAL and natural variation in CRP may contribute to these findings. Conversely, treatment effect heterogeneity appears less pronounced for mean PPD, %BOP, and %PD ≤3 mm, potentially due to greater treatment effects in patients with more severe periodontitis and reduced measurement error in these parameters.

Aim: This study aimed to investigate the association of periodontitis with biological aging and to assess potential causality using Mendelian randomization (MR).

Methods: A cross-sectional study with 9558 participants from the National Health and Nutrition Examination Survey (2009-2014) was conducted. Age acceleration (BioAgeAccel and PhenoAgeAccel) was calculated from clinical biomarkers and their discrepancies with chronological age. Two-sample MR analysis was performed using data from a large-scale genome-wide association study and UK Biobank.

Results: Periodontitis was associated with increased biological aging, with 0.57-year (95% CI: 0.28-0.86, p < .001) increases in BioAgeAccel and 0.41-year (95% CI: 0.04-0.78, p = .034) increases in PhenoAgeAccel. Subgroup analysis found significantly stronger associations in males for BioAgeAccele (P_INTERACTION = .006), and pronounced associations in young adults (p_interaction = .023), individuals with normal body mass index (p_interaction = .015), and current smokers (p_interaction = .016) for PehonAgeAccel. MR analysis did not provide strong evidence for a causal effect of periodontitis on biological aging (BioAgeAccel: IVW β = 0.008, 95% CI: -0.018 to 0.034, p = .553 and PhenoAgeAccel: IVW β = 0.016, 95% CI: -0.042 to 0.074, p = .585).

Conclusion: This study identified the association of periodontitis and its severity with accelerated aging, suggesting periodontal health could be a possible method in personalized preventive and therapeutic strategies of biological aging.