Journal of periodontal research最新文献

Aim: 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.

Methods: 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.

Results: 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.

Conclusions: 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.

Aim: 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).

Methods: 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.

Results: 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.

Conclusion: 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.

Aims: The goal of this study was to explore new candidate genes and pathogenesis mechanisms of nonsyndromic hereditary gingival fibromatosis (nsHGF) and to provide an experimental basis for the diagnosis of nsHGF.

Methods: Whole-exome sequencing (WES) was performed on peripheral blood DNA from three nsHGF family members to screen for new candidate genes, and Sanger sequencing and related databases were used to verify the pathogenicity of this gene deficiency. Moreover, the effects of gene deficiency on the biological characteristics of human gingival fibroblasts (HGFs) were evaluated via cell proliferation assays, extracellular matrix (ECM) deposition detection, cell apoptosis and cell cycle assessment, cell migration and gene expression analyses.

Results: A novel missense mutation in dual-specificity phosphatase 8 (DUSP8, c.1348C>T, p.R450C), which is in the nsHGF-related GINGF4 locus, was identified via WES analysis. A functional study revealed that knocking down DUSP8 expression increased cell proliferation, cell migration and the expression of profibrotic factors (particularly COL1A1), inhibited cell apoptosis, and ultimately resulted in nsHGF. Similarly, this DUSP8 mutation inhibited the expression of the encoded protein and promoted cell proliferation and the expression of profibrotic factors. In addition, both DUSP8 knockdown and DUSP8 mutation induced nsHGF by accelerating glycolysis and panlysine lactylation (Kla) to promote cell proliferation and the expression of ECM-related factors.

Conclusion: DUSP8 deficiency might be a novel pathogenic factor that contributes to nsHGF.

Aim: To test a BiO-Optimizing Site Targeted (BOOST) approach to periodontal regeneration by the adjunctive use of locally delivered doxycycline (DOX) 2 weeks prior to minimally invasive surgery in terms of clinical and radiographic outcomes at 1 year.

Methods: For this randomized clinical trial, stage III/IV periodontitis patients presenting sites with intrabony defects and bleeding on probing (BoP+) after steps 1-2 of periodontal treatment were included. Sites were treated via subgingival instrumentation with or without a BOOST approach by local DOX. After 2 weeks, defects were accessed by minimally invasive surgical technique with xenograft and amelogenins. Primary (clinical attachment level [CAL] gain) and secondary (probing pocket depth [PPD] reduction, composite outcomes, radiographic bone defect fill) outcomes were assessed at 12 months.

Results: Sixty patients completed the study (30 on each group). BOOST led to lower preoperative BoP (p < 0.001) and better wound healing after surgery (p = 0.027). Both groups showed clinical and radiographic improvements at 1 year, with significant differences in mean CAL gain (4.1 ± 1.9 vs. 3.2 ± 2.0 mm; p = 0.019) and PPD reduction (4.4 ± 1.8 vs. 3.6 ± 1.9 mm; p = 0.040) favoring the test group. BOOST group also achieved higher composite outcome measure (PPD ≤ 4 mm and CAL gain ≥ 3; 83.3% vs. 46.7%; p = 0.006), pocket closure (PPD ≤ 3 mm or 4 mm BoP-; 83.3% vs. 60.0%; p = 0.045), and defect fill (3.5 ± 1.2 vs. 2.7 ± 1.3 mm; p < 0.001) compared to the control group.

Conclusion: A BOOST approach by local doxycycline 2 weeks before surgery enhanced the local inflammatory control prior to periodontal regeneration and post-operative early wound healing, yielding to improved clinical and radiographic outcomes at 1 year.

Trial registration: ClinicalTrials.gov identifier: NCT05878353.

Aim: The correlation between periodontitis and colorectal cancer (CRC) has drawn widespread attention. However, how periodontitis affects CRC progression remains unclear.

Methods: C57BL/6 mice were used to establish experimental periodontitis and CRC model. Histological alterations of periodontium and colon were observed by hematoxylin and eosin staining. Micro-computed tomography (micro-CT) was applied to evaluate alveolar bone loss (ABL). Tumor growth was detected by immunofluorescence. Gut bacteria were analyzed using 16S rRNA sequencing. Gas chromatography-mass spectrometry (GC-MS) was performed to observe the alterations of gut microbial metabolites. The detection of associated pathways was carried out using quantitative real-time PCR (qRT-PCR).

Results: Experimental periodontitis significantly induced increases in tumor number in mice with CRC. Double immunofluorescence for Ki67 and β-catenin, as well as Cyclin D1 and β-catenin, indicated that experimental periodontitis observably promoted tumor growth. 16S rRNA sequencing and untargeted metabolomics analysis displayed that experimental periodontitis altered gut microbial community and metabolite profiles in CRC mice. Notably, we found that experimental periodontitis dramatically increased the level of three oncometabolites (serotonin, adenosine, and spermine) in mice with CRC.

Conclusion: Alterations of gut microbial community and metabolites might be relevant in experimental periodontitis deteriorating CRC.

Aim: To assess tissue perfusion changes and wound healing biomarker levels after root coverage procedures with coronally advanced flap in combination with the cross-linked xenogeneic collagen matrix (CCMX), loaded either with a placebo or recombinant human platelet-derived growth factor-BB (rhPDGF).

Methods: This study was designed as a secondary analysis from a previously published clinical trial, and it assessed the tissue perfusion changes over 6 months around multiple gingival recession defects, treated with either with CCMX alone (control) or with CCMX + rhPDGF (test). High frequency Doppler ultrasonography (HFUS) scans were obtained at sites of interest at baseline, 2 weeks, 3 months, and 6 months after surgery. Dynamic tissue perfusion measurements (DTPMs) were performed at the midfacial, interproximal, and transverse aspects of the teeth by an operator, blinded to treatment allocation, using a software package. The expression of different wound healing biomarkers from the gingival crevicular fluid was also assessed.

Results: The regression analyses showed similar tissue perfusion changes between the two groups throughout the majority of the 6 months. DTPMs at 2 weeks showed the test group to have significantly higher perfusion relief intensity (pRI, p < 0.001), mean perfused area (pA, p < 0.001), mean blood flow intensity (FI_mean, p = 0.021), and total blood flow intensity (FI_tot, p = 0.021) at the graft region of interest (ROI) compared to control sites. The test sites also exhibited significantly greater pA (p = 0.033) and blood flow intensity "blue" (FI_blue, meaning flow away from the transducer, p = 0.035) at the level of the flap compared to the control sites. At 2 weeks, FI_blue of the graft was directly correlated with the final mean root coverage (p = 0.008) and complete root coverage (p = 0.003). FI_mean and FI_tot of the graft exhibited a direct correlation with volume gain at 6 months (p = 0.031 for both parameters). The final GT gain was correlated to the early DTPMs (pA and FI_blue) of the graft and the flap. The two groups exhibited different expressions of IL-1β, PDFG-BB, and VEGF over 3 months, with the 1-week levels of PDGF-BB that were associated with time to recovery.

Conclusions: HFUS allowed exquisite assessment of tissue perfusion occurring at the entire surgical reconstructive regions and also within the flap and the graft. Sites treated with CCMX + rhPDGF exhibited higher DTPMs, primarily within the graft and flap ROIs at the 2-week timepoint compared to sites augmented with CCMX + saline. Early DTPMs at the graft and flap ROIs showed associations with PROMs and the final clinical outcomes.

Trial registration: ClinicalTrials.gov: NCT04462237.

Aim: This prospective cohort study aimed to evaluate the incidence and risk/protective factors of peri-implantitis over time.

Methods: A university-representative cohort was evaluated at baseline and after a mean follow-up time of 3.9 years. The main outcome was the incidence of peri-implantitis, defined as bone loss > 1 mm between the two examinations in implants showing bleeding on probing. Putative risk/protective factors assessed at baseline were tested through multilevel (mixed-effects) logistic regression analyses.

Results: A total of 73 patients with 322 implants were included. During the follow-up period, 14 implants (4.3%) were lost in 9 patients (12.3%). Incidence of peri-implantitis was observed in 22.2% of patients and 9.4% of implants. In the final multilevel multiple logistic regression model, the following factors were associated with occurrence of peri-implantitis: periodontitis severity (stage IV periodontitis: OR = 41.29; 95% CI: 4.10-415.54), periodontal bone loss/age ratio (> 1: OR = 8.87; 95% CI: 1.47-53.73), smoking (current smokers: OR = 7.84; 95% CI: 1.83-33.50), sleep duration (> 7 h: OR = 19.97; 95% CI: 1.69-236.39), implant location (incisor: OR = 60.60; 95% CI: 4.04-908.33), restoration type (full-arch fixed restorations: OR = 89.84; 95% CI: 3.66-2202.97), and restoration margin location (juxta-marginal: OR = 14.17; 95% CI: 1.20-166.76). Keratinized tissue width assessed at baseline was not associated with incidence of peri-implantitis.

Conclusion: Approximately one in five patients and one in 10 implants experienced incident peri-implantitis over a nearly four-year period. Periodontitis (Stage IV and Grade C), lifestyles (smoking and sleep duration), implant location, and prosthetic factors (restoration type and margin location) emerged as risk factors for peri-implantitis.

Aim: The clinical outcomes of a variety of surgical procedures highly depend on tissue repair and show high variability among patients. There is a gap in the literature on how the host inflammatory response, the microbiome, and the interplay between them can influence oral mucosa healing. In this pilot study, we aimed to evaluate the microbiome and biomarkers profiles in patients who had desired versus undesired wound healing in the palatal mucosa.

Methods: Seventeen patients underwent a free gingival graft (FGG) for socket preservation. Palatal wound closure (WC) and epithelization (EPT) were assessed clinically. Biofilm from the palatal wound was collected before the surgical procedure and 3, 7, 14, and 30 days postoperatively. The inflammatory exudate was sampled on Days 3 and 7. At 14 days posttreatment, patients were classified into two groups based on EPT rates: (1) undesired healing (UH) and (2) desired healing (DH).

Results: No difference was observed in alfa diversity over time or between groups. In beta diversity, both UH and DH showed microbiome changes on Days 3-7 and 7, respectively, compared with the baseline (p = 0.01), returning to its initial condition 30 days later. There was a trend toward a different microbiome profile between groups on Day 7 (p = 0.08). Bacterium composition in DH showed a balance between healthy species and oral pathogens over time, whereas UH composition was characterized by microorganisms correlated with epithelium invasion/cytotoxicity; virulence factor upregulation; and oral diseases, such as periodontitis and aphthous stomatitis, until Day 30. UH showed an increase in IL-6, MCP-1, and MIP-1α over time, and DH showed a decrease in TIMP-1, IL-1β, and MIP-1α. On Days 3 and 7, MIP-1α and MMP-2 showed greater concentrations of DH in the intergroup assessment, and MCP-1 increased on Day 7 in UH.

Conclusion: Specific microbiome/inflammatory profiles are associated with DH and UH.

Trial registration: NCT05171400.

Aim: To evaluate the diagnostic accuracy of microbiome-derived biomarkers for periodontitis in oral fluids (saliva and subgingival samples).

Methods: This systematic review followed PRISMA guidelines. Electronic searches were performed across multiple databases from December 2022 to November 2024. Subgroup analyses, divided into saliva and subgingival samples, were performed using the Random Effects Model (REM), while individual biomarker sensitivity and specificity were evaluated through the Bivariate Random-Effects Model (BREM).

Results: Ten studies were included, stratified by sample type. In the saliva group, Porphyromonas gingivalis, Tannerella forsythia and Prevotella intermedia demonstrated the highest diagnostic accuracy, with sensitivities reaching 89.2%, 89.2% and 86.5%, and specificities of 94.6%, 86.5% and 83.8%, respectively, achieving AUC values above 0.80. Porphyromonas gingivalis was further analysed using BREM, with the Summary Receiver Operating Characteristic (SROC) curve indicating a combined sensitivity and specificity of 84.2% and 85.4%, with an AUC of 0.864. In the subgingival group, biomarkers such as endotoxin activity and combined bacterial biomarkers (5 bacterial species) displayed the highest diagnostic performance, with sensitivities of 90.6% and 85.1% and specificities of 87.9% and 100%, respectively, and AUC values of 0.93 and 0.88.

Conclusion: Microbiome-derived biomarkers show good clinical utility for improving diagnoses of periodontitis, offering high specificity and sensitivity. Future research should focus on standardising methodologies, increasing sample sizes, and including diverse populations to validate these findings, thereby improving diagnostic precision and facilitating the screening methods for the onset of periodontitis and dysbiotic activity.

Aim: Ultrasonography (US) has shown accuracy in imaging healthy periodontium. This study aims to evaluate the feasibility and accuracy of US for estimating dimensions of inflamed periodontium induced by ligature and bacteria.

Methods: Periodontal tissues of maxillary as well as mandibular premolars and molars in six female mini pigs were treated with ligature and three strains of bacteria for 4-10 weeks. Before euthanization, the periodontium was imaged with US. After euthanization, cone-beam computed tomography (CBCT) scans and histology were performed. Soft and hard tissue measurements by calibrated and masked examiners from US, CBCT, and histology were statistically compared.

Results: Seventy-one histological samples with corresponding CBCT and US scans were available for analysis. Overall, there was a good to excellent agreement between histology and US (ICC: 0.77-0.96) for parameters such as Soft Tissue Thickness (STT), Gingival Recession, Crestal Bone Thickness (CBT), and the bone-to-cemento-enamel junction (B-CEJ) distance. However, discrepancies were observed for STT at 3 mm below the CEJ and Soft Tissue Height (STH) (ICC: 0.44 and 0.54, respectively). CBCT showed lower agreement with histology, particularly for thin CBT (< 1 mm), with an ICC of 0.20, compared to 0.90 for US vs. histology. CBCT failed to identify crestal bone in 14 cases when the crestal bone was thin. Notably, CBCT results differed more from histological measurements than US in assessing B-CEJ and thin CBT.

Conclusion: US demonstrated substantial potential as a transformative tool for periodontal diagnostics, exhibiting high agreement with histology in determining critical parameters. Compared to CBCT, US offered advantages, particularly in cases with thin crestal bone.