Journal of periodontal research最新文献

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.

In 2025, the Journal of Periodontal Research proudly celebrates its 60th anniversary. On this occasion, after more than 50 years, we are transitioning to 12 issues per year [1]. Together with this milestone, we introduce one of the exciting initiatives marking the journal's new era: a series of Perspective Articles under the theme “The Past, The Present, The Future”. This series will feature contributions from the “giants” of our field and will serve as a unique opening to each issue of the Journal of Periodontal Research.

The series commences with an insightful contribution from one of the most influential figures ever in periodontology: Professor Jan Lindhe. This manuscript stems from a memorable conversation we shared over tea and biscuits at his home in May 2024. During this magnetic interview, I was transported back in time to relive the pivotal moments that have shaped periodontology, vividly recounted from his extraordinary memory. At the same time, I was struck by his revolutionary mindset, as he continues to challenge established dogmas and share his visionary ideas for the future of our discipline.

I am delighted to share the essence of this unforgettable encounter, which holds a special place in my heart. I hope that this manuscript not only transports readers to that tea-and-biscuits moment, but also ignites a burst of inspiration from the past, present, and future of periodontology.

Mario Romandini

Editor-in-Chief

Journal of Periodontal Research

The launch of the Journal of Periodontal Research in the mid-1960s marked a transformative moment for periodontology. At the time, Dr. Harald Löe—an influential periodontist and researcher—recognized the need for a dedicated journal that would treat periodontology as a research-driven discipline. Unlike the clinical-focused publications of the time, which centered on practical tips and specific geographic areas, this new journal aimed to elevate scientific inquiry in periodontology, positioning the field as a serious, research-based specialty globally. For many years, the Journal of Periodontal Research earned its place as one of the leading journals in dentistry worldwide.

My own career began alongside the Journal of Periodontal Research. My first article as lead author was published in JPR in 1966 [2], the second ever piece published in the journal. Periodontology was still finding its footing then, and at that time, the main focus was on understanding the etiology of periodontitis.

This first issue of 2025 marks a significant milestone in the history of the Journal of Periodontal Research as, after more than 50 years, we will transition to a monthly release format (12 issues per year). This change reflects the journal's growth and its commitment to delivering the latest findings in periodontal research with increased frequency and accessibility. With this new phase, we wanted a brand new cover for the journal that would symbolize not only this advancement but also our dedication to bridging the past, present, and future of periodontal science.

Every element in the cover illustration has been carefully crafted to represent the diverse scope of the journal. The left image on periodontal regeneration highlights one of our central missions: advancing tissue engineering and supporting the quest for bone, periodontal, soft tissue, and even tooth regeneration. The central image focuses on peri-implant tissues, with dental implants facing the challenge of peri-implantitis and restorative elements, emphasizing the journal's growing focus on implantology and related sciences. This fresh clinical focus is complemented by a presence of periodontal plastic surgery, the pinnacle of clinical periodontal artistry.

The circular insets invite readers to explore deeper layers of periodontal basic sciences, connecting them with themes such as immunology and microbiology, which have always characterized the journal's legacy. These elements reflect our dedication to advancing knowledge of periodontal diseases pathogenesis and therapeutic innovation, linking the journal to its storied past. The insets additionally embody our interest on histology, biomaterials and cell biology, underscoring our commitment to publishing research across multiple scientific dimensions of periodontal and peri-implant health. Beyond these visible themes, the cover also represents areas equally vital to the journal, such as epidemiology, preclinical research, clinical trials, novel digital technologies, and public health research. By combining both visual and conceptual symbolism, we aim to capture the full breadth of the Journal of Periodontal Research's scope and purpose.

This new cover serves both as a strong statement of the editorial scopes and as a tribute to the enduring legacy and forward-looking vision of our journal. We hope it resonates with our readers, researchers, and the periodontal community as a beacon of inspiration for future discoveries in our field.

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.

Aim: Compliance with plaque control measures in open interdental spaces, an essential element in management of periodontitis, is reported to be poor. Mobile health (mHealth) approach is an effective approach for behavior change. This study aimed to assess the effectiveness of mHealth in improving plaque control in type 2 embrasures.

Methods: Stage II or III, grade B periodontitis patients (n = 76) with type 2 embrasures were enrolled. Phase I therapy was provided in both groups. In the control group, interdental brushing instructions were given only at baseline and follow-up appointments. In the test group, interdental brushing was also reinforced by regular text messages for 3 months. Clinical parameters including plaque index (PI), papillary bleeding index (PBI), probing pocket depth (PPD), clinical attachment level (CAL), gingival index (GI), bleeding on probing (BOP), and interdental papillary height (IPH) were measured at baseline, 1, 3, and 6 months.

Results: Intergroup comparison from baseline to 6 months showed a statistically significant difference (p < 0.05) between groups in all parameters with more reduction in mean values in test group. Intergroup comparison from 3 to 6 months showed a statistically significant difference (p < 0.05) in mean values of PI, PBI, GI, PPD, CAL, and IPH with higher reduction in test group. Intragroup comparison from 3 to 6 months showed statistically significant reduction in mean values in PI, PBI, PPD, CAL, and IPH only in test group (p < 0.05).

Conclusion: Cue to action through mobile text messages effectively augments compliance with the use of interdental brush, improves plaque control, and manages stage II or stage III periodontitis following subgingival instrumentation.

Trial registration: ClinicalTrials.gov identifier: NCT05565404.