OBJECTIVES: To investigate the effects of periodontitis induced by Prevotella nigrescens (Pn) combined with ligation on cognitive functions in mice. METHODS: Twenty-four C57BL/6J mice were randomly divided into control group, ligation group, and ligation + Pn treatment (P+Pn) group. Experimental periodontitis was induced by silk ligation of the first molars followed by topical application of Pn for 6 weeks. After modeling, alveolar bone resorption was assessed using micro-CT and histological analysis. Learning and memory abilities of the mice were evaluated using open field test (OFT), novel object recognition test (NORT), and Morris water maze test (MWM). Seven weeks after the start of modeling, the mice were sacrificed for examining histopathological changes in the hippocampus using HE and Nissl staining. RESULTS: After 6 weeks of molar ligation, micro-CT revealed horizontal alveolar bone resorption and furcation exposure in the mice, and histological analysis showed apical migration of the junctional epithelium, epithelial ridge hyperplasia, and lymphocyte infiltration, and these changes were obviously worsened in P+Pn group. Alveolar bone height decreased significantly in both ligation groups compared to the control group. Cognitive tests showed that the mice in both of the ligation groups traveled shorter distances in OFT, showed reduced novel object preference in NORT, and exhibited longer escape latencies in MWM, and the mice in P+Pn group had significantly poorer performances in the tests. Histologically, obvious neuronal cytoplasmic degeneration, necrosis, nuclear pyknosis, vacuolation, and reduced Nissl bodies and viable neurons were observed in the hippocampal regions of the mice in the two ligation groups. CONCLUSIONS Pn infection aggravates alveolar bone destruction, accelerates necrosis and causes morphological abnormalities of neuronal cells in the hippocampus to reduce cognitive functions of mice with periodontitis.
Animals ; Periodontitis/microbiology* ; Mice ; Mice, Inbred C57BL ; Cognition ; Alveolar Bone Loss ; Hippocampus/pathology* ; Male ; Inflammation ; Maze Learning

Hypoxemia is a common pathological state characterized by low oxygen saturation in the blood. This condition compromises mucosal barrier integrity particularly in the gut and oral cavity. However, the mechanisms underlying this association remain unclear. This study used periodontitis as a model to investigate the role of platelet activation in oral mucosal immunopathology under hypoxic conditions. Hypoxia upregulated methyltransferase-like protein 4 (METTL4) expression in platelets, resulting in N⁶-methyladenine modification of mitochondrial DNA (mtDNA). This modification impaired mitochondrial transcriptional factor A-dependent cytosolic mtDNA degradation, leading to cytosolic mtDNA accumulation. Excess cytosolic mt-DNA aberrantly activated the cGAS-STING pathway in platelets. This resulted in excessive platelet activation and neutrophil extracellular trap formation that ultimately exacerbated periodontitis. Targeting platelet METTL4 and its downstream pathways offers a potential strategy for managing oral mucosa immunopathology. Further research is needed to examine its broader implications for mucosal inflammation under hypoxic conditions.
DNA, Mitochondrial/metabolism* ; Mouth Mucosa/pathology* ; Hypoxia/immunology* ; Methyltransferases/metabolism* ; Blood Platelets/metabolism* ; Animals ; Periodontitis/immunology* ; Humans ; Platelet Activation ; Mice

Smoking is a well-established risk factor for periodontitis, yet the precise mechanisms by which smoking contributes to periodontal disease remain poorly understood. Recent advances in spatial transcriptomics have enabled a deeper exploration of the periodontal tissue microenvironment at single-cell resolution, offering new opportunities to investigate these mechanisms. In this study, we utilized Visium HD single-cell spatial transcriptomics to profile gingival tissues from 12 individuals, including those with periodontitis, those with smoking-associated periodontitis, and healthy controls. Our analysis revealed that smoking disrupts the epithelial barrier integrity, induces fibroblast alterations, and dysregulates fibroblast-epithelial cell communication, thereby exacerbating periodontitis. The spatial analysis showed that endothelial cells and macrophages are in close proximity and interact, which further promotes the progression of smoking-induced periodontal disease. Importantly, we found that targeting the endothelial CXCL12 signalling pathway in smoking-associated periodontitis reduced the proinflammatory macrophage phenotype, alleviated epithelial inflammation, and reduced alveolar bone resorption. These findings provide novel insights into the pathogenesis of smoking-associated periodontitis and highlight the potential of targeting the endothelial-macrophage interaction as a therapeutic strategy. Furthermore, this study establishes an essential information resource for investigating the effects of smoking on periodontitis, providing a foundation for future research and therapeutic development for this prevalent and debilitating disease.
Humans ; Gingiva/cytology* ; Smoking/adverse effects* ; Male ; Periodontitis/pathology* ; Single-Cell Analysis ; Female ; Adult ; Middle Aged ; Macrophages ; Fibroblasts ; Endothelial Cells ; Case-Control Studies ; Chemokine CXCL12/metabolism*

OBJECTIVES: This study aimed to explore the therapeutic effect and mechanism of ginsenoside Rb3 on experimental periodontitis and bone resorption in rats. METHODS: Male SD rats were randomly divided into a control group, a ligation group, an Rb3 group, and a doxycycline (Dox) group for in vivo experiments. A periodontitis model was established by ligating the maxillary second molar, and samples were collected after 3 weeks of drug treatment. Micro-CT assessment of alveolar bone resorption was performed, and hematoxylin-eosin (HE) staining was used to observe pathological changes in periodontal and visceral tissues. Tartrate resistant acid phosphatase (TRAP) staining was applied to detect the formation of osteoclasts in periodontal tissues, and enzyme-linked immunosorbent assay (ELISA) was adopted to detect the serum levels of interleukin (IL)-6, IL-8, immunoglobulin (Ig)M, and IgG. Quantitative polymerase chain reaction (qPCR) was employed to detect the expression of factors related to gingival inflammation and osteoclast formation. Immunofluorescence staining was used to detect phospho-extracellular signal-regulated kinase (p-ERK) expression. In vitro experiments were conducted by pretreating RAW264.7 cells with drugs and adding lipopolysaccharides (LPS) stimulation from Porphyromonas gingivalis (P. gingivalis). IL-1β and IL-6 mRNA expression was detected by qPCR, and Western blot was used to detect the effect of Rb3 on the mitogen-activated protein kinases (MAPKs) signaling pathway. RESULTS: Compared with the control group, the ligation group showed significant periodontitis and bone resorption. Compared with the ligation group, the Rb3 group showed a decrease in alveolar bone resorption and osteoclast formation; p-ERK/ERK ratio, IL-1β, IL-6, and nuclear factor of activated T cells (NFATc1) mRNA levels and downstream gene expression in periodontal tissues; serum IL-6, IL-8, IgG, and IgM levels. Rb3 reduced IL-8 and IL-1β mRNA expression levels and p-ERK/ERK and p-p38 MAPK/p38 MAPK ratios in RAW264.7 cells induced by P. gingivalis LPS stimulation. CONCLUSIONS Rb3 inhibits inflammation and bone resorption in experimental periodontitis in rats. Compared with Dox, Rb3 has better effects in inhibiting pro-inflammatory factors and osteoclast gene expression and may exert anti-inflammatory effects by activating the MAPK signaling pathway.
Animals ; Ginsenosides/therapeutic use* ; Rats, Sprague-Dawley ; Male ; Periodontitis/pathology* ; Rats ; Osteoclasts/drug effects* ; Interleukin-1beta/metabolism* ; Interleukin-6/blood* ; Mice ; Alveolar Bone Loss ; Interleukin-8/blood* ; Immunoglobulin G/blood* ; RAW 264.7 Cells ; Transcription Factors

Dens invaginatus is a rare developmental anomaly of the teeth that is caused by the infolding of enamel organs or the penetration of their proliferations into dental papillae before calcification has occurred. The presence of double dens invaginatus is extremely rare. This paper describes the use of cone beam computed tomography in the evaluation of a maxillary lateral incisor with double dens invaginatus and periapical periodontitis. The tooth was treated through microscopic root canal therapy. The tooth was free of clinical symptoms, and the periradicular lesion narrowed during the follow-up period of 1 year.
Humans ; Dental Pulp Cavity/abnormalities* ; Dens in Dente/pathology* ; Incisor/pathology* ; Root Canal Therapy ; Periapical Periodontitis/pathology*

OBJECTIVES: To investigate the effect of peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) on liver injury induced by periodontitis in rats. METHODS: Twenty-four male Wistar rats were randomly divided into two groups: control group and periodontitis group, twelve per group. In periodontitis group, the periodontitis models were established for the maxillary first molars in rats by means of "wire ligation+vaccinationwith RESULTS: The probing depth, tooth mobility and sulcus bleeding index in periodontitis group were significantly higher than that in control group. HE staining showed in periodontitis group, hepatic cords ranged disorderly and there were vacuoles in cells and inflammatory cells infiltrated in liver tissues of rats, and there was no obvious abnormality in control group. The qRT-PCR results showed that the mRNA expression levels of CONCLUSIONS PGC-1α may be involved in the process of periodontitis-induced liver injury in rats.
Animals ; Liver/injuries* ; Male ; PPAR gamma ; Periodontitis/pathology* ; Rats ; Rats, Wistar

OBJECTIVE: To investigate the relationship between periodontal disease and subclinical atherosclerosis in middle-aged and older adults in Shijingshan community of Beijing. METHODS: In 2005-2010, a total of 830 middle-aged and older adults were recruited from Shijingshan community of Beijing, who were divided into two groups by severity of periodontitis. A questionnaire, periodontal examination, blood biochemical examination, carotid intima-media thickness (CIMT), including common carotid artery (CCA-IMT), internal carotid artery (ICA-IMT) and carotid bifurcation (CB-IMT), were measured of each subject. The associations of periodontitis with CIMT was evaluated by multivariable Logistic regression analysis and analysis of covariance, adjusted for age, gender, education level, hypertension, hyperlipidemia, obesity, smoking, drinking, and diabetes. And then anther definition of periodontitis (mild periodontitis: percentage of AL≥3 mm <10%; moderate periodontitis: percentage of AL≥3 mm 10%-30%; severe periodontitis: percentage of AL≥3 mm ≥30%) was used to investigate the hypotheses that different classification of periodontitis would affect results. RESULTS: The subjects with moderate-severe periodontitis were characterized by significantly higher levels of CCA-IMT, ICA-IMT, CB-IMT and mean CIMT than the mild group. In the univariate analysis, moderate-severe periodontitis was associated with an increased risk of ICA-IMT>0.9 mm (adjusted OR=1.230, 95% CI: 1.058-1.452, P=0.031). Furthermore, moderate periodontitis was associated with an increased risk of CB-IMT>0.9 mm (adjusted OR: 1.297, 95%CI: 1.117-1.753, P=0.011) and severe periodontitis was associated with an increased risk of CB-IMT>0.9 mm (adjusted OR=1.771, 95%CI: 1.176-3.503, P=0.042) according to another classification of periodontitis. CONCLUSION Our data provided evidence that periodontitis was associated with CIMT among middle-aged and older adults in Shijingshan community of Beijing and different periodontitis classification would affect the results.
Aged ; Atherosclerosis/complications* ; Beijing ; Carotid Arteries ; Carotid Artery, Common ; Carotid Artery, Internal ; Carotid Intima-Media Thickness ; Chronic Periodontitis/pathology* ; Diabetes Mellitus ; Humans ; Middle Aged ; Risk Factors

Inflammation from chronic and acute infections of distal organs and tissues such as periodontitis is a risk factor for atherosclerotic vascular processes. Recently, a new model of atherosclerosis with vascular pathologies was developed in the Mongolian gerbil. In this study, we attempted to develop a model of ligature-induced periodontitis in gerbils and compared the characteristics of that periodontitis model with that in rats and mice. Each gerbil, rat, and mouse was randomly assigned to groups of control and periodontitis. A thread was placed around the cervix of the right and left first molars in the mandible with knots placed on the mesial side of each molar. At day 14 after the ligation, the animals were sacrificed and their mandibles were dissected. To measure alveolar bone loss along with inflammation, histopathological and micro-CT analyses were carried out. Gerbils showed tooth characteristics of deeper gingival crevice, longer cusp, longer root trunk and shorter root than those of rats and mice. The increased CEJ-ABC distance in distal and PDL area in furcation was also observed in ligated gerbils. An inflammatory response in the connective tissue under the junctional epithelium was also shown in all the animals. As a result, we confirmed the induction of periodontitis by ligature in the gerbils. We therefore consider the gerbil to be a useful model for investigating relationship between periodontitis and vascular disease in the same animal.
Alveolar Bone Loss ; Animals* ; Atherosclerosis ; Cervix Uteri ; Connective Tissue ; Epithelial Attachment ; Female ; Gerbillinae* ; Inflammation ; Ligation ; Mandible ; Mice ; Models, Animal* ; Molar ; Pathology ; Periodontitis* ; Rats ; Risk Factors ; Tooth ; Vascular Diseases

Substantial evidence supports the relationship between chronic inflammation and cancer development. Numerous studies suggest that chronic inflammatory disease, such as periodontitis, contributes to head and neck squamous cell carcinoma development. Oral squamous cell carcinoma (OSCC) is the most common malignant tumor in the oral and maxillofacial regions. Porphyromonas gingivalis, one of the most important pathogens in association with periodontal disease, might have a potential correlation with OSCC. Along with the development of molecular biological techniques, the association between Porphyromonas gingivalis and OSCC has been greatly emphasized in recent years. This review summarizes the association between these variables and the potential mechanisms involved in such relationship.
Carcinoma, Squamous Cell ; pathology ; Humans ; Mouth Neoplasms ; pathology ; Periodontal Diseases ; Periodontitis ; Porphyromonas gingivalis ; Research

This study assessed the roles of chronic stress (CS) in the stimulation of the sympathetic nervous system and explored the underlying mechanisms of periodontitis. Using an animal model of periodontitis and CS, the expression of tyrosine hydroxylase (TH) and the protein levels of the alpha1-adrenergic receptor (alpha1-AR) and beta2-adrenergic receptor (beta2-AR) were assessed. Furthermore, human periodontal ligament fibroblasts (HPDLFs) were stimulated with lipopolysaccharide (LPS) to mimic the process of inflammation. The proliferation of the HPDLFs and the expression of alpha1-AR and beta2-AR were assessed. The inflammatory-related cytokines interleukin (IL)-1beta, IL-6 and IL-8 were detected after pretreatment with the alpha1/beta2-AR blockers phentolamine/propranolol, both in vitro and in vivo. Results show that periodontitis under CS conditions enhanced the expression of TH, alpha1-AR and beta2-AR. Phentolamine significantly reduced the inflammatory cytokine levels. Furthermore, we observed a marked decrease in HPDLF proliferation and the increased expression of alpha1-ARfollowing LPS pretreatment. Pretreatment with phentolamine dramatically ameliorated LPS-inhibited cell proliferation. In addition, the blocking of alpha1-ARsignaling also hindered the upregulation of the inflammatory-related cytokines IL-1beta, IL-6 and IL-8. These results suggest that CS can significantly enhance the pathological progression of periodontitis by an alpha1-adrenergic signaling-mediated inflammatory response. We have identified a potential therapeutic target for the treatment of periodontal disease, particularly in those patients suffering from concurrent CS.
Adrenergic alpha-1 Receptor Antagonists/*therapeutic use ; Animals ; Cells, Cultured ; Cytokines/immunology ; Fibroblasts/immunology/pathology ; Humans ; Lipopolysaccharides/administration & dosage/immunology ; Male ; Periodontal Ligament/cytology/immunology/pathology ; Periodontitis/*drug therapy/*etiology/immunology/pathology ; Phentolamine/*therapeutic use ; Rats ; Rats, Wistar ; Receptors, Adrenergic, alpha-1/analysis/*immunology ; Signal Transduction/drug effects ; *Stress, Physiological/drug effects ; Tyrosine 3-Monooxygenase/analysis/immunology