Protective efficacy and related mechanism of deinoxanthin in experimental animal and cell models of periodontitis
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE305324 | GEO | 2026/02/13
REPOSITORIES: GEO
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Project description:Single cell analysis of PDL cells in ligature-induced periodontitis: The periodontal ligament (PDL) is a fibrillar connective tissue that lies between the alveolar bone and the tooth and is composed of highly specialized extracellular matrix (ECM) molecules and a heterogeneous population of cells that are responsible for collagen formation, immune response, bone formation, and chewing force sensation. Type VI collagen (COL6), a widely distributed ECM molecule, plays a critical role in the structural integrity and mechanical properties of various tissues including muscle, tendon, bone, cartilage, and skin. However, its role in the PDL remains largely unknown. Our study shows that deficiency of COL6 impairs PDL fibrogenesis and exacerbates tissue destruction in ligature-induced periodontitis (LIP). We found that COL6 deficient mice exhibited increased bone loss and degraded PDL in LIP and that fibroblasts expressing high levels of Col6α2 are pivotal in ECM organization and cell-ECM interactions. Moreover, COL6 deficiency in the PDL led to an increased number of fibroblasts geared towards the inflammatory response. We also observed that cultured COL6 deficient fibroblasts from the PDL exhibited decreased expression of genes related to collagen fiber metabolism and ECM organization, and migration and proliferation. Our findings suggest that COL6 plays a crucial role in the PDL, influencing fibroblast function in fibrogenesis and affecting the immune response in periodontitis. These insights could advance our understanding of the molecular mechanisms underlying PDL maturation and periodontal disease.
2024-06-24 | GSE255695 | GEO
Project description:Periodontitis (PD) as a chronic inflammatory disease instigated by periodontal pathogenic bacteria and mediated by the host immune response, resulting in the destruction of supporting periodontal tissue and tooth loss in adults. Constructing an injectable delivery system that allows for sustained drug release within periodontal pockets to continuously eliminate pathogenic bacteria, reduce periodontal inflammation, and promote periodontal tissue regeneration is an effective strategy for periodontitis treatment. Here, we explore the therapeutic potential and underlying mechanisms of curcumin-loaded Pickering emulsion (PE-CUR) in periodontitis treatment. The Pickering emulsion formulation offers an effective delivery system, enhancing curcumin's bioavailability and therapeutic efficacy. In vitro studies, we demonstrate that the PE-CUR exhibit excellent biocompatibility and anti-inflammatory property by elimination of reactive oxygen species (ROS). In addition, PE-CUR significantly eliminate key periodontal pathogens, including Porphyromonas gingivalis (P. gingivalis) and Staphylococcus aureus (S. aureus). In a rat model of periodontitis, PE-CUR significantly attenuates periodontal tissue inflammation and alveolar bone loss, indicating a protective effect against periodontal tissue destruction. Mechanistically, PE-CUR promotes the expression of anti-inflammatory factors and inhibits the release of pro-inflammatory factors by regulating macrophage polarization from M1 to M2 and modulating the MAPK and PI3K-AKT signaling pathway. Furthermore, PE-CUR decreases the formation of osteoclasts as well as stimulates the activation and differentiation of osteoblasts successively, thereby ameliorating the periodontal inflammation and promoting the alveolar bone regeneration. Overall, our findings elucidate the therapeutic mechanisms of PE-CUR in periodontitis, suggesting its potential as a promising treatment strategy warranting further clinical investigation.
2024-08-16 | GSE274645 | GEO
Project description:Background: Periodontitis is a chronic inflammatory disease and macrophages play a pivotal role in the progression of periodontitis. Mesenchymal stem cells (MSCs) have emerged as potential therapeutic agents for the treatment of periodontitis due to their immunomodulatory properties and capacity for tissue regeneration. Compared to conventionally derived MSCs, induced pluripotent stem cell-derived MSCs (iMSCs) offer distinct advantages as promising candidates for MSC-based therapies, owing to their non-invasive acquisition methods and virtually unlimited availability. This study aims to investigate the effects and mechanisms of iMSCs in modulating macrophage polarization and alleviating periodontitis-related alveolar bone loss. Methods: iMSCs were generated from iPSCs and characterized for differentiation potential. The effects of iMSCs on macrophage polarization were evaluated using THP-1-derived macrophages under inflammatory conditions (LPS and IFN-γ stimulation). Co-culture assays, cytokine analysis, reactive oxygen species (ROS) detection, transcriptomic analysis, flow cytometry, reverse transcription-quantitative polymerase chain reaction (RT-qPCR), and western blot analysis were performed to elucidate the underlying mechanisms. The therapeutic potential of iMSCs was assessed in a ligature-induced periodontitis mouse model using micro-CT, histological analysis, and immunofluorescence staining. Results: iMSCs inhibit M1 macrophage polarization through the suppression of the NF-κB signaling pathway. Additionally, iMSCs reduce the production of pro-inflammatory cytokines (IL-1β, IL-17) and reactive oxygen species (ROS), while enhancing the secretion of anti-inflammatory cytokines (IL-10) and growth factors (VEGF), thereby improving the inflammatory microenvironment. Under inflammatory conditions, iMSCs preserve the osteogenic potential of periodontal ligament stem cells (PDLSCs) and alleviate alveolar bone loss in mice with periodontitis. In vivo, iMSCs reduce the number of M1 macrophages and inhibit the activation of NF-κB in periodontal tissues, supporting their anti-inflammatory and immunomodulatory effects. Conclusion: iMSCs demonstrate significant therapeutic potential in periodontitis by modulating macrophage polarization, reducing oxidative stress, and mitigating alveolar bone loss associated with the disease. These findings provide new insights into the mechanisms of iMSCs and their application as cell-based therapies for periodontal diseases.
2025-04-01 | GSE283726 | GEO
Project description:Dysbiosis of subgingival microbiome promotes the growth of periodontopathogens and the development of periodontitis, an irreversible chronic inflammatory disease. Untreated periodontitis leads to the destruction of connective tissues, alveolar bone resorption and ultimately to tooth loss. Periodontitis has been associated with inflammatory metabolic diseases such as type 2 diabetes. While periodontitis-induced inflammation is a key player in both, the development of subgingival microbiome dysbiosis and in the host-microbiome interaction, the effects of hyperglycemia on the regulation of the host genes controlling the inflammatory response and the host-microbiome interaction are still scarce. We investigated the impacts of a hyperglycemic microenvironment on the inflammatory response and gene expression of a gingival fibroblasts-macrophages coculture model stimulated with dysbiotic subgingival microbiomes. A coculture model composed of immortalized human gingival fibroblasts overlaid with U937 macrophages-likes cells were stimulated with subgingival microbiome collected from four healthy donors and four patients with periodontitis. Pro-inflammatory cytokines and matrix metalloproteinase were measured by a Luminex assay while the coculture RNA was submitted to a microarray analysis. Subgingival microbiomes were submitted to 16s rRNA gene sequencing. Data were analyzed by using an advanced multi-omics bioinformatic data integration model. Our results showed that krt76, krt27, pnma5, mansc4, rab41, thoc6, tm6sf2, and znf506 as well as the pro-inflammatory cytokines IL-1, GM-CSF, FGF2, IL-10, the metalloproteinases MMP3 and MMP8, and bacteria from the ASV 105, ASV 211, ASV 299, Prevotella, Campylobacter and Fretibacterium genera are key correlated variables contributing to periodontitis-induced inflammatory response in a hyperglycemic microenvironment. To conclude, our multi-omics integration analysis unveiled unique differentially interrelated bacterial genera, genes and pro-inflammatory cytokines involved in the regulation of the inflammatory response in a hyperglycemic microenvironment. These data also highlight the importance of considering hyperglycemic conditions in the development of new drugs or treatments for periodontal disease in link with type 2 diabetes.
2023-05-31 | GSE222883 | GEO
Project description:Periodontitis is a chronic inflammatory disease resulting from a dysbiosis of the dental biofilm and a dysregulated host response in susceptible individuals. It is characterized by periodontal attachment destruction, bone resorption, and eventual tooth loss. Salivary biomarkers have been sought to predict and prevent periodontitis. This comparative study analyzed the salivary proteome of 30 individuals with chronic periodontitis (CP) and 10 with periodontal health (PH), and correlated specific proteins with clinical parameters of disease by using mass spectrometry. Stimulated whole saliva was obtained and pooled for 5 healthy controls and 15 CP patients, precipitated with TCA, digested enzymatically with trypsin and analyzed by an LTQ Orbitrap Velos equipped with a nanoelectrospray ion source. A wide range of salivary proteins of various functions was significantly reduced in CP individuals, whereas salivary acidic proline-rich phosphoprotein, submaxillary gland androgen-regulated protein, histatin, fatty acid-binding protein, thioredoxin, and cystatin were predominant in diseased patients and correlated significantly with signs of periodontal attachment loss and inflammation. Specific salivary proteins were associated with PH and CP. These differences in salivary proteome profiles may contribute to the identification of disease indicators or signatures and the improvement of periodontal diagnosis.
2020-05-20 | PXD015024 | Pride
Project description:Neutrophil recruitment and activation are hallmarks of the prevalent inflammatory disease, periodontitis. However, the mechanisms by which neutrophils contribute to in inflammatory bone destruction remain unclear. Herein, we document that neutrophil extracellular traps (NETs) have a direct role in mediating inflammatory pathology. In an established animal model of periodontitis, we demonstrate that genetic or pharmacologic inhibition of NETs formation, or removal of NETs by DNase-Ⅰ, alleviates inflammatory bone loss in vivo. Investigating the mechanisms by which NETs drive periodontal inflammation, we find that extracellular histones have a direct role in disease progression. Consistent with findings in animal models, histones bearing classic NET-associated post-translational modifications are correlated with disease severity and are significantly elevated in local lesions and systemic circulation of patients with periodontitis. Our work reveals NETs-associated components as pathogenic mediators, potential biomarkers, and therapeutic targets for periodontitis.
2023-05-23 | GSE228021 | GEO
Project description:To investigate the function of different tissues in the pathogenesis, we established a modified mouse ligature-induced periodontitis model, supporting the separation of the maxillae into gingiva, peri-root, and bone tissue. After setting the right molars as the non-ligature control side and the left molars as the ligature side, we performed gene expression profiling and gene enrichment analysis using data obtained from RNA-seq of sixteen individuals after 11 days of induction (32 samples in total). Four individuals were WT mice, and another four were Il33-deficient mice. Sample of peri-root tissues and bone tissues from these mice were compared separately to explore the role of Il33 in the chronicity of periodontitis, especially its function in periodontal ligament and bone tissue.
2024-02-23 | GSE244931 | GEO
Project description:Phase 1: The whole saliva samples were obtained from 66 systemically healthy subjects consisting of patients with chronic periodontitis (CP), generalized aggressive periodontitis (G-AgP), gingivitis and individuals with periodontal health. The use of humans for study satisfied the requirements of the Ege University Institutional Review Board (Ethics number 16-12.1/16) and and was conducted in accordance with the guidelines of the World Medical Association Declaration of Helsinki. It is confirmed that this cross-sectional study conforms to STROBE guidelines for observational studies. Complete medical and dental histories were taken from all participants. Systemic exclusion criteria were the presence of cardiovascular and respiratory diseases, diabetes mellitus, HIV infection, systemic inflammatory conditions or non-plaque-induced oral inflammatory conditions, immunosuppressive chemotherapy, and current pregnancy or lactation. Smoking status was also recorded. None of the patients had taken medication such as antibiotics or anti-inflammatory drugs that could affect their periodontal status for at least 6 months before the study. Patients eligible for the study returned to the clinic for clinical measurement screening one-week after being pre-screened. Before being enrolled in the study, participants provided written and informed consent to use their saliva samples and individual data for scientific purposes. The clinical periodontal indices including probing depth (PPD), clinical attachment level (CAL), plaque index (PI) and bleeding on probing (BOP) were recorded by a manual periodontal probe by a trained and calibrated examiner (V.O.O). The extent and severity of alveolar bone support were evaluated radiographically in each patient. The participants were classified into four groups based on their periodontal conditions according to the criteria proposed by the 1999 International Workshop for a Classification of Periodontal Diseases and Conditions (REF). Generalized Aggressive Periodontitis (G-AgP): The G-AgP group included 17 patients with ≥16 teeth. The patients had a non- contributory medical history and demonstrated with an early age of clinical manifestations with a generalized pattern of rapid attachment loss and bone destruction. These individuals had minimum of CAL ≥ 5 mm and PD ≥ 6 mm on eight or more teeth; at least three of these were other than central incisors or first molars. Radiographic bone loss was above ≥ 30 % of root length affecting ≥3 permanent teeth other than first molars and incisors. Generalized Chronic Periodontitis (CP): The CP group included 17 patients with severe generalized chronic periodontitis. These individuals had a minimum four non-adjacent teeth with sites with CAL ≥ 5 mm and PPD ≥ 6 mm, and ≥50 % alveolar bone loss in at least two quadrants which was commensurate with the amount of plaque accumulation. Phase 2: We aimed to develop SRM-based workflow for detecting and quantitating the relative abundance of the candidate proteins in an independent saliva cohort . 82 subjects (48 females and 34 males; age range 24-59 years) were recruited for the study at the Department of Periodontology, School of Dentistry, Adnan Menderes University, Aydın, Turkey. Ethical clearance was obtained from the Ethics Committee of the School of Medicine, Ege University with the protocol number ((Ethics number 70198063-050.06.04). Each participant gave written and verbal informed consent after the purpose and procedures of the study were explained. A dental and medical history was compiled for all subjects as detailed in phase 1 and participants were clustered into four groups according to the criteria proposed by the 1999 International Workshop for a Classification of Periodontal Diseases and Conditions as detailed at Phase 1
2018-04-10 | PXD007535 | Pride
Project description:In this study, an α2(VI) deficient mouse (Col6α2-KO) model was used to examine the role of Type VI collagen in oral tissues. To examine bone properties, µCT was employed, and bone volume and bone mineral density (BMD) was measured in oral tissues. To further investigate its molecular basis, proteome analysis was performed using protein extracted from alveolar bone. In addition, alveolar bone loss progression was evaluated with a periodontitis induced model. µCT analysis showed the Col6α2- KO mice had less volume of alveolar bone, dentin and dental pulp, while the width of periodontal ligament (PDL) was greater than WT. The BMD in alveolar bone and dentin were elevated in Col6α2-KO mice compared with WT. Our proteome analysis showed significant changes in proteins related to ECM organization and elevation of proteins associated with biomineralization in the Col6α2-KO mice. In induced periodontitis, Col6α2-KO mice had greater alveolar bone loss compared to WT. In conclusion, Type VI collagen has role in controlling biomineralization in alveolar bone and that changes in the ECM of alveolar bone could be associated with greater bone loss from periodontitis.
2022-11-21 | PXD037422 | Pride
Project description:Genetic defects in neutrophil function or trafficking are highly associated with oral inflammation and periodontitis. The leukocyte NADPH oxidase enzymes complex is a multi-subunit enzyme that has been described to play important immunomodulatory roles in limiting the inflammatory responses of neutrophils and macrophages. Here, we determined the impact of loss of NADPH oxidase dependent reactive oxygen species (ROS) generation in gingival inflammatory responses using a model of ligature induced murine periodontitis.
2024-04-23 | GSE184556 | GEO