Journal of periodontal research最新文献

Aim: Periodontitis is a chronic inflammatory disease initiated by dysbiosis of the local microbial community. As a non-specific phosphodiesterase inhibitor, dipyridamole features anti-oxidant and anti-inflammatory properties. This study aimed to investigate the effects of dipyridamole in an experimental rat model of periodontitis.

Methods: Thirty rats were divided randomly into three groups (n = 10): non-ligature group (NL), ligature-induced periodontitis group (L), and ligature-induced periodontitis with dipyridamole administered group (L + D). All rats were euthanized on Day 14. Alveolar bone resorption was analyzed by microcomputed tomography. The mRNA levels of Il1b, Il6, tumor necrosis factor alpha (Tnfa), and inducible nitric oxide synthase (iNos) in gingival tissue were assessed by real-time quantitative polymerase chain reaction (qRT-PCR). Inflammation level, osteoclasts, and macrophages infiltration were analyzed histologically. RAW264.7 macrophages were stimulated with Porphyromonas gingivalis lipopolysaccharide (P.g. LPS) to induce M1 polarization. Different concentration of dipyridamole (0/2/10 μM) was added simultaneously. To explore the role of PKA/PKG pathways, RAW 264.7 macrophages were pretreated with 10 μM H-89 (PKA inhibitor) or 1 μM KT-5823 (PKG inhibitor), respectively. Expression of pro-inflammatory cytokines and M1 markers were detected by qRT-PCR, ELISA, and flow cytometry.

Results: Dipyridamole administration reduced alveolar bone loss, protein levels of inflammatory cytokines, and osteoclastogenesis in rats with experimental periodontitis. It also showed a tendency to decrease mRNA levels of Il1b, Il6, and Tnfa but without significant differences in gingival tissues. Moreover, the infiltration of macrophage and M1 macrophage polarization in gingival tissue of periodontitis rats were inhibited by dipyridamole administration. In addition, dipyridamole could downregulate the gene expression of Il1b and Tnfa, as well as the protein level of TNF-α, CD86, and iNOS in RAW264.7 treated with P.g. LPS. When PKA/PKG pathways were blocked, the suppression of TNF-α, CD86, and iNOS was reversed significantly.

Conclusion: Dipyridamole alleviated experimental periodontitis in rat models by regulating M1 polarization via activation of PKA/PKG pathways and emerges as a hopeful remedy for periodontitis.

Aim: To investigate additional factors contributing to the pathophysiology of chemotherapy-induced oral mucositis and periodontitis beyond the systemic immune suppression caused by the chemotherapeutic agent 5-Fluorouracil (5-FU).

Methods: 5-Fluorouracil was topically delivered to the non-keratinized, rapidly proliferating junctional epithelium (JE) surrounding the dentition, and acts as an immunologic and functional barrier to bacterial ingression. Various techniques, including EdU incorporation, quantitative immunohistochemistry (qIHC), histology, enzymatic activity assays, and micro-computed tomographic (μCT) imaging, were employed to analyze the JE at multiple time points following topical 5-FU treatment. Systemic 5-FU delivery was used for comparison, and all 5-FU treated tissues were compared to vehicle-treated controls.

Results: We first showed that systemic 5-FU blocked mitotic activity that rapidly led to JE atrophy. This atrophy was accompanied by suppression of the immune system. We then demonstrated that topical 5-FU delivery effectively inhibited cell proliferation in the JE. Quantitative immunohistochemical (qIHC) analyses further demonstrated a progressive breakdown in JE barrier functions following topical 5-FU. CBC analyses confirmed that topical 5-FU did not alter the innate immune system but did suppress the local immune response of the JE. The longer-term consequences of this disruption in JE barrier functions were significant alveolar bone loss and an increase in porosity. Together, these results document the essential requirement for rapid JE cell proliferation to maintain homeostasis of the periodontium.

Conclusions: The reduction of cell division in the JE due to 5-FU treatment directly compromises both its structural integrity and immune surveillance capabilities, contributing to the destruction of periodontal hard tissues.

Aim: This study aimed to evaluate and compare the results of combination therapy involving bone grafting and two different resorbable collagen membranes in 1-, 2- and 3-wall infrabony defects.

Methods: A total of 174 patients with infrabony defects (≥ 7 mm periodontal probing depth) were randomized to receive deproteinized bovine bone mineral (DBBM) with either a native porcine non-crosslinked collagen membrane (N-CM, control, n = 87) or a novel porcine crosslinked collagen membrane (C-CM, test, n = 87). Clinical parameters, including periodontal probing depth (PPD), clinical attachment level (CAL), and gingival recession (GR), were recorded at baseline, 12 weeks, and 24 weeks. Radiographic evaluations measured linear bone gain (LBG) and percentage of bone fill (%BF) at baseline and 24 weeks. Generalized Estimating Equations (GEE) were used to identify predictors of clinical outcomes. The primary outcome was the total effectiveness rate based on a composite outcome score integrating clinical and radiographic parameters at 24 weeks.

Results: One hundred seventy three patients completed the study. At 24 weeks, mean improvements in PPD were 4.17 ± 1.48 mm and 4.16 ± 0.97 mm for the control and test groups, respectively, while CAL gains were 3.69 ± 1.32 mm and 3.60 ± 1.81 mm. Radiographic linear bone gain was 3.12 ± 2.19 mm in the control group and 3.00 ± 1.92 mm in the test group. Subgroup analysis showed trends favoring the test group for PPD (p = 0.046) and CAL (p = 0.042) improvements in 1-wall defects. The total effectiveness rate was 96.55% in the control group and 95.35% in the test group, with a difference of -1.2% (95% CI: -5.88% to 3.47%). Among those with effective results, the test group had a higher proportion achieving significantly effective outcomes compared to the control group (96.5% vs. 86.2%, p = 0.032). Regression analysis identified treatment group, defect morphology, and baseline defect depth as significant predictors of PPD and CAL outcomes.

Conclusion: The novel porcine crosslinked collagen membrane demonstrated non-inferiority to the native non-crosslinked membrane in periodontal regeneration. Regression analysis highlighted defect morphology and baseline defect depth as key predictors of outcomes, while subgroup analysis suggested potential advantages of the C-CM in challenging defect morphologies, such as 1-wall defects. These findings provide valuable insights into clinical decision-making. However, the findings are limited by the short-term nature of the study (24 weeks), and further long-term investigations are needed to confirm these preliminary results and assess their clinical relevance.

Trial registration: ClinicalTrials.gov identifier: NCT04851847.

Aim: To investigate whether trained immunity occurs in gingival fibroblasts (GFs) and its relationship to the persistence of inflammation in periodontitis.

Methods: Periodontally healthy and inflammatory gingival fibroblasts (HGFs and IGFs) were cultured through continuous adherence subculture of tissue blocks. Trained immunity in HGFs was evaluated via a classic in vitro model, with relevant markers assessed via enzyme-linked immunosorbent assay, lactate content assay, glycolytic rate assay, and chromatin immunoprecipitation. A histone methyltransferase blocker and a PI3K inhibitor were added to investigate the mechanisms underlying trained immunity. The relationship between trained immunity and periodontitis was further examined via immunofluorescence staining and chromatin immunoprecipitation on IGFs.

Results: Compared with untrained cells, GFs trained with Porphyromonas gingivalis-lipopolysaccharide (P. gingivalis-LPS) exhibited a significant increase in IL-6 and TNF-α secretion, enhanced glycolytic metabolism, and enriched mono-methylation of lysine 4 on histone H3 (H3K4me1) at the enhancer regions of TNF-α and IL-6. The addition of a histone methyltransferase blocker and a PI3K inhibitor greatly reduced trained immunity. Additionally, the response of IGFs to P. gingivalis-LPS stimulation and their epigenetic modifications were similar to those observed in trained HGFs.

Conclusion: This study novelly discovered that both P. gingivalis-LPS-stimulated HGFs and IGFs in periodontitis acquired trained immunity. Following P. gingivalis-LPS stimulation, HGFs underwent metabolic and epigenetic changes via the PI3K/AKT pathway, with these epigenetic changes also observed in IGFs. This finding suggests that trained immunity in GFs may be a key mechanism underlying the recurrence and persistence of periodontitis.

Aim: Salivary content is regarded as a powerful diagnostic window for oral and systemic diseases and the proteomic profile could be useful to distinguish between different periodontal conditions. The aim of the present systematic review was to assess distinctive salivary proteins identified through untargeted proteomics in periodontitis patients compared to periodontally healthy and gingivitis subjects, as well as to provide a qualitative methodological assessment of the current literature.

Methods: Relevant studies identified from Medline via PubMed, Scopus, Embase, and Cochrane Library databases were retrieved to answer the following PECO question: "In systemically healthy individuals, are there any differences in salivary protein expression profiles assessed in proteomics studies between patients with periodontitis and periodontally healthy or gingivitis subjects?" Moreover, diagnostic utility of the identified markers was sought via a targeted literature search and further quantitative assessment. A modified version of the QUADAOMICS tool was used for the quality assessment of the included studies.

Results: After screening 461 relevant articles, a total of 13 studies were selected. The number of identified discriminant salivary proteins ranged from 2 to 4161. However, it was possible to identify proteins that were consistently over- or under-expressed in periodontitis patients in at least 3 studies. Among these, complement C3, profilin-1, SA100A8, and fibrinogen were consistently reported as increased in periodontitis, while cystatin-SN and leukocyte elastase inhibitor were more elevated in periodontally healthy controls. Only 4 studies reported diagnostic accuracy measures, with SA100A8 showing an area under the curve of 0.71 (95% CI: 0.66-0.75) in meta-analysis.

Conclusions: Untargeted proteomics techniques identified some key biological molecules which were consistently reported to be over- or under-expressed in periodontitis. These findings could be useful to support novel candidate biomarkers for periodontitis. The high level of heterogeneity in methods and reporting urge to develop standardized protocols to be implemented in this research field (PROSPERO CRD42022299826).

Aims: Periodontitis is a chronic disease affecting adult oral health. Transient receptor potential vanilloid 1 (TRPV1) expression is shown to upregulate in many inflammatory diseases. Nevertheless, its biological potential along with the molecular mechanism in periodontitis is unclear. Our study aimed to explore the biological role and underlying signaling pathway of TRPV1 in periodontitis.

Methods: In the current research, human periodontal ligament stem cells (hPDLSCs) were stimulated by lipopolysaccharide (LPS) to induce inflammatory conditions in vitro. In vivo, the periodontitis mouse model was built by ligating the gingival sulcus of male C57BL/6J mice. Thereafter, the proliferation, apoptosis, inflammation, and oxidative stress-related processes were assessed.

Results: We found that LPS induced apoptosis and inflammation in hPDLCs, along with oxidative stress, while simultaneously inhibiting hPDLC proliferation (p < 0.05). Notably, TRPV1 expression was elevated in LPS-treated hPDLSCs and gingival samples from patients with periodontitis. Interestingly, the increase in TRPV1 expression induced by Capsaicin, a TRPV1 agonist, inhibited cell proliferation while promoting LPS-stimulated apoptosis, inflammation, and oxidative stress in hPDLSCs (p < 0.01). In contrast, inhibition of TRPV1 expression using Capsazepine, a TRPV1 inhibitor, produced opposite effects (p < 0.01). In vivo experiments revealed that inhibition of TRPV1 attenuated ligation-induced periodontitis in mice, as evidenced by enhanced oxidative stress, inflammatory response, and elevated apoptosis (p < 0.01). Additionally, rescue assays indicated that TRPV1 promoted periodontitis-associated tissue inflammation and oxidative damage via activating the STAT3 signaling pathway (p < 0.01).

Conclusion: Our study demonstrates that TRPV1 expression is high in periodontitis and facilitates periodontitis-associated tissue inflammation and oxidative damage by regulating STAT3 signaling pathway, which implies that TRPV1 may represent a new therapeutic target for periodontitis.

Aims: Chronic periodontitis is the sixth most prevalent disease worldwide and the leading cause of tooth loss in adults. With growing attention on the role of inflammatory and immune responses in its pathogenesis, there is an urgent need to evaluate host-modulatory agents. Non-steroidal anti-inflammatory drugs (NSAIDs) drugs play a crucial role in managing inflammatory conditions. This study examined the repercussions of long-term naproxen use in a periodontal inflammation model known for causing significant inflammation, disrupting epithelial and connective tissue attachment and leading to alveolar bone destruction.

Methods: Thirty BALB/c mice were treated with naproxen for 60 days or left untreated. From Day 30, an LPS solution was injected into gingival tissues three times per week for four weeks. This model enables LPS control over the inflammatory stimulus intensity throughout the experimental period, leading to chronic inflammation development involving both innate and adaptive immunity. The liver, stomach and maxillae were submitted to histological analysis. The oxidative damage was determined by measuring lipid peroxidation (LPO) in plasma and gingiva. The activities of myeloperoxidase (MPO), eosinophil peroxidase (EPO), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and levels of leukotriene B4, the interleukin (IL)-1β, TNF-α, IL-4, IL-5, IL-10, the chemokine CCL11 were also assessed in the gingival tissues.

Results: The results indicated that none of the groups displayed any indications of liver damage or alterations; however, the NPx treatment led to severe gastric damage. In contrast, the treatment alleviated periodontal inflammation, resulting in a reduction of chronic and acute inflammatory cell infiltration and prevention of connective tissue loss in the gingival tissue. Additionally, the treatment increased the activities of endogenous antioxidant enzymes SOD, CAT and GPx, as well as the IL-10 cytokine, while decreasing the levels of leukotriene B4, TNF-α, IL-4 and IL-5. Furthermore, the activities of MPO, EPO and LPO were reduced in the treated groups.

Conclusion: These results suggest that NPx effectively inhibits periodontal inflammation in an inflammatory periodontal model. However, the harmful gastric effects dramatically limit its long-term use.

Aim: To investigate the role of lipopolysaccharide (LPS) from Porphyromonas gingivalis and miR-155-5p-enriched exosomes in the formation of foam cells and the occurrence of carotid atherosclerosis (CAS).

Methods: The CAS tissue samples and plasma from the healthy control group or patients undergoing periodontitis without CAS and with CAS were collected at the Xuanwu Hospital, Capital Medical University. The expression level of miR-155-5p was evaluated by immunofluorescent analysis and qRT-PCR. Oil red O staining and lipid accumulation assays were performed to explore the effects of LPS and miR-155-5p on mouse macrophage Raw264.7 and human monocytes THP-1. The expression levels of lipid-regulated genes were detected by qRT-PCR. Dual-luciferase reporter gene assay and DET1 overexpressed or inhibited Raw264.7 cells were used to verify the target gene of exosomal miR-155-5p. ApoE^-/- mice were used to confirm the auxo-action of atherosclerosis from exosomal miR-155-5p in vivo, and LAL assay was used to detect the LPS content.

Results: miR-155-5p was higher in patients with periodontitis and CAS plasma exosomes than those in patients without CAS. The expression of miR-155-5p was significantly increased in CAS tissues compared with Normal tissues, and the expression level of miR-155-5p was associated with lipid-regulated genes in CAS tissues. MiR-155-5p-enriched exosomes accelerated lipid accumulation in macrophage-like cells and promoted the activity of lipid-accumulation genes by targeting DET1. In ApoE^-/- mice, circulating miR-155-5p-enriched exosomes captured LPS, and the LPS-laden exosomes conferred plasma access for LPS, triggering the formation of foam cells and the occurrence of CAS.

Conclusion: miR-155-5p enriched exosomes capture and escort LPS to the atherosclerotic sites, licensing the formation of foam cells and thus promoting CAS.