Periodontal disease is predominantly caused by the pathogenic bacterium Porphyromonas gingivalis that produces inflammation-inducing factors in the host. Eucommia ulmoides is a plant native to China that has been reported to reduce blood pressure, promote weight loss, and exhibit anti-inflammatory effects. Geniposidic acid (GPA) is the major component of E. ulmoides. Herein, we investigated the effects of GPA on P. gingivalis-induced periodontitis by measuring the inflammatory responses in human gingival epithelial cells (HGECs) after P. gingivalis stimulation and GPA addition in a P. gingivalis-induced periodontitis mouse model. We found that GPA addition suppressed interleukin (IL)-6 mRNA induction (33.8% suppression), IL-6 production (69.2% suppression), toll-like receptor (TLR) 2 induction, and mitogen-activated protein kinase (MAPK) phosphorylation in HGECs stimulated by P. gingivalis. Inoculation of mice with GPA inhibited P. gingivalis-induced alveolar bone resorption (25.6% suppression) by suppressing IL-6 and TLR2 production in the serum and gingiva. GPA suppressed osteoclast differentiation of bone marrow cells induced by M-CSF and sRANKL in mice (56.7% suppression). GPA also suppressed the mRNA expression of OSCAR, NFATc1, c-Fos, cathepsin K, and DC-STAMP. In summary, GPA exerts an anti-inflammatory effect on periodontal tissue and may be effective in preventing periodontal disease.

This study aimed to evaluate cytokine profiling in a periapical lesion to provide a rationale for future treatment strategies for periapical lesions. Thirteen samples of exudative fluid were collected from such a lesion directly through the root canal. Cytokine profiling was performed using the Bio-Plex system. CXCL10 (C-X-C motif chemokine ligand 10, IP10) was found to be elevated in apical exudates of patients exhibiting favorable healing. To evaluate the role of CXCL10 in cell migration, a Transwell assay was conducted using bone marrow-derived mononuclear cells (BMMCs). Different types of cytokines were detected from the samples of periapical lesion at the initial visit. However, cytokine production varied across patient samples. Release of interleukin (IL)-1β, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12, IL-13, IL-17, granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage colony-stimulating factor (GM-CSF), interferon gamma (IFN-γ), monocyte chemoattractant protein (MCP)-1, macrophage inflammatory protein (MIP)-1α, MIP-1β, and tumor necrosis factor (TNF)-α showed differential expression. Comparison of cytokine profiles indicated that cytokine production was variable before and after root canal treatment. In vitro, CXCL10 significantly improved BMMC migration in a dose-dependent manner, supporting clinical findings that elevated CXCL10 levels are associated with favorable healing in apical lesions. Although this study was limited by the small sample size and exploratory design, the cytokine profile of periapical lesions may be useful for assessing the condition of periapical lesions and modulating the immune response to bacterial infection.

Aggressive periodontitis causes rapid destruction of periodontal tissue. It occurs at a young age with familial clustering. We report on the first time on molecular and cellular basis of a Mendelian form of autosomal dominant aggressive periodontitis. Monoallelic mutations in the monocyte to macrophage differentiation-associated 2 (MMD2) gene, encoding MMD2, in two Japanese families with autosomal dominant aggressive periodontitis are identified. Mutations, c.347 C>T (p.A116V) and c.377 G>C (p.R126P) in MMD2, disturbed fMLP-induced activation of Ras/ERK signaling. Additionally, abnormalities in the proteins of Golgi apparatus, a crucial contributor to innate immune signaling pathways, were identified in patients’ neutrophils. The knock-in and knockout mice exhibited alveolar bone loss by ligature-induced periodontitis, along with impaired fMLP-induced chemotaxis, as found in the patients with MMD2 mutation. Our studies revealed that monoallelic mutations in MMD2 underlie the impairment of neutrophil chemotaxis, which leads to the development of autosomal dominant aggressive periodontitis.

Background/Objectives: The optimal management of periodontal treatment in patients receiving direct oral anticoagulants (DOACs) remains poorly established, and bleeding concerns may lead clinicians to delay or limit treatment. We evaluated the clinical efficacy and safety of nonsurgical periodontal treatment in patients receiving DOAC therapy. Methods: This retrospective study included 67 patients receiving continuous DOAC therapy (edoxaban, apixaban, dabigatran, or rivaroxaban) who underwent nonsurgical periodontal treatment without drug discontinuation. Pocket probing depth, bleeding on probing, the periodontal inflamed surface area (PISA), the periodontal epithelial surface area (PESA), and serum inflammatory cytokine levels were evaluated. A ligature-induced-periodontitis mouse model was also used to assess the effect of apixaban on alveolar bone loss. Results: Nonsurgical periodontal treatment significantly reduced the PISA (42.9%) and PESA (10.8%) in the overall DOAC cohort, with no postoperative bleeding complications. Significant reductions in periodontal parameters were seen in the edoxaban (PISA: 44.2%, PESA: 10.9% reduction), apixaban (PISA: 45.6%, PESA: 11.7% reduction), and dabigatran (PISA: 61.3%, PESA: 16.1% reduction) groups, with no significant changes in the rivaroxaban group. Baseline PISA was positively correlated with baseline serum levels of interleukin-4 (r = 0.33), interleukin-1 beta (r = 0.29), interleukin-6 (r = 0.25), and interleukin-10 (r = 0.30). In the mouse model, apixaban administration did not aggravate ligature-induced alveolar bone loss. Conclusions: Basic periodontal treatment appears to be safe and effective for patients prescribed DOACs and may reduce local periodontal inflammation, resulting in systemic inflammatory burden. These findings support proactive periodontal intervention in patients receiving DOAC therapy, regardless of the specific anticoagulant used.