The Role of Gingival Fibroblasts in the Pathogenesis of Periodontitis

Journal of Dental Research, Journal Year: 2023, Volume and Issue: 102(5), P. 489 - 496

Published: March 8, 2023

Gingival fibroblasts (GFs) are essential components of the periodontium, which responsible for maintenance tissue structure and integrity. However, physiological role GFs is not restricted to production remodeling extracellular matrix. also act as sentinel cells that modulate immune response oral pathogens invading gingival tissue. As an important “nonclassical” component innate system, respond bacteria damage-related signals by producing cytokines, chemokines, other inflammatory mediators. Although activation supports elimination resolution inflammation, their uncontrolled or excessive may promote inflammation bone destruction. This occurs in periodontitis, a chronic disease periodontium initiated sustained dysbiosis. In inflamed tissue, acquire imprinted proinflammatory phenotypes growth inflammophilic pathogens, stimulate osteoclastogenesis, contribute chronicity inflammation. this review, we discuss biological functions healthy highlighting recent studies provide insight into pathogenesis periodontal diseases. We draw parallels with recently discovered fibroblast populations identified tissues roles health disease. knowledge should be used future discover more about diseases, especially identify therapeutic strategies targeting pathological interactions system.

Language: Английский

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Multifunctionalized and Dual‐Crosslinked Hydrogel Promotes Inflammation Resolution and Bone Regeneration via NLRP3 Inhibition in Periodontitis

Small Structures, Journal Year: 2024, Volume and Issue: 5(3)

Published: Feb. 5, 2024

Alveolar bone resorption caused by bacteria‐induced periodontitis remains challenging due to sustained inflammation. Periodontal pathogens like Porphyromonas gingivalis launch the primed signal of NOD‐like receptor family pyrin domain‐containing 3 (NLRP3) inflammasome in macrophages; consequent overproduction proinflammatory cytokines and reactive oxygen species (ROS) leads tissue destruction. This provides potential targets for a new therapeutic strategy. Herein, multifunctionalized dual‐crosslinked hydrogel pGM/cPL@NI with NLRP3 inhibitor MCC950 loaded is prepared. Driven strategic functionalization gelatin methacryloyl ε ‐poly‐lysine phenylboronic acid catechol, respectively, containing dynamic photo‐crosslinking networks demonstrates superior mechanical strength stimuli‐responsive behavior, as well overwhelmed performance bacteria killing ROS scavenging. Crucially, restores compromised osteogenesis specifically suppressing cytokine cascade triggered activation promoting anti‐inflammatory polarization macrophages. Collectively, presents robust an effective “cocktail therapy” combining antibacterial, antioxidant, inflammation resolution, regenerative functions. The present study reveals underlying mechanism bacterial‐immune‐regeneration extended approach periodontal engineering.

Language: Английский

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Variational graph autoencoder for reconstructed transcriptomic data associated with NLRP3 mediated pyroptosis in periodontitis

Scientific Reports, Journal Year: 2025, Volume and Issue: 15(1)

Published: Jan. 14, 2025

The NLRP3 inflammasome, regulated by TLR4, plays a pivotal role in periodontitis mediating inflammatory cytokine release and bone loss induced Porphyromonas gingivalis. Periodontal disease creates hypoxic environment, favoring anaerobic bacteria survival exacerbating inflammation. inflammasome triggers pyroptosis, programmed cell death that amplifies inflammation tissue damage. This study evaluates the efficacy of Variational Graph Autoencoders (VGAEs) reconstructing gene data related to NLRP3-mediated pyroptosis periodontitis. NCBI GEO dataset GSE262663, containing three samples with without hypoxia exposure, was analyzed using unsupervised K-means clustering. method identifies natural groupings within biological prior labels. VGAE, deep learning model, captures complex graph relationships for tasks like link prediction edge detection. VGAE model demonstrated exceptional performance an accuracy 99.42% perfect precision. While it identified 5,820 false negatives, indicating conservative approach, accurately predicted 4,080 out 9,900 positive samples. model's latent space distribution differed significantly from original data, suggesting tightly clustered representation expression patterns. clustering show promise analysis structure reconstruction research.

Language: Английский

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Transcutaneous electrical acupoint stimulation attenuated neuroinflammation and oxidative stress by activating SIRT1-induced signaling pathway in MCAO/R rat models

Experimental Neurology, Journal Year: 2023, Volume and Issue: 373, P. 114658 - 114658

Published: Dec. 21, 2023

Language: Английский

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Kynurenic acid inhibits macrophage pyroptosis by suppressing ROS production via activation of the NRF2 pathway

Molecular Medicine Reports, Journal Year: 2023, Volume and Issue: 28(5)

Published: Sept. 22, 2023

Macrophage pyroptosis and related inflammatory responses play an important role in periodontitis. Kynurenic acid (KA) is hypothesized to have anti‑inflammatory potential, but whether KA can inhibit macrophage the underlying mechanisms remain unclear. Lipopolysaccharide (LPS) was used induce THP‑1‑derived macrophages. or ML385 pretreat macrophages, after which, cell viability, NOD‑like receptor protein 3 (NLRP3) inflammasome‑related expression, oxidative stress levels nuclear factor erythroid 2‑related 2 (NRF2) expression were measured. The results showed that improved LPS‑induced decrease viability lactate dehydrogenase release. prevented THP‑1 induced by LPS reducing of NLRP3, Gasdermin‑D, Caspase1, decreased factors. suppressed NLRP3 inflammasome activation inhibiting ROS overproduction increasing Heme Oxygenase 1 glutathione levels. Moreover, promoted NRF2 translocation from cytoplasm nucleus. In addition, anti‑pyroptotic antioxidant effects reversed inhibition NRF2. present study, it found significantly LPS. It further demonstrated mediated pathway.

Language: Английский

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Insight into the role of macrophages in periodontitis restoration and development

Virulence, Journal Year: 2024, Volume and Issue: 15(1)

Published: Nov. 13, 2024

Periodontitis is one of the chronic diseases that have greatest impact on human health, and it associated with several other diseases. Tissue damage periodontitis often connected immune response. Immune cells are a crucial component system directly involved in during inflammatory phase disease. Macrophages, as key system, responsible for defence, antigen presentation phagocytosis healthy tissue. They also closely linked to development resolution periodontitis, through mechanisms such macrophage polarization, pattern recognition receptors recognition, efferocytosis, Specialized Pro-resolving Mediators (SPMs) production. Additionally, apoptosis autophagy known play role recovery periodontitis. This review aims investigate aforementioned more detail identify novel therapeutic approaches

Language: Английский

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Programmed Cell Death Tunes Periodontitis

Oral Diseases, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 23, 2025

ABSTRACT Objective To review current knowledge of the various processes programmed cell death and their roles in immunoregulation periodontitis. Methods Relevant literature PubMed, Medline, Scopus databases was searched, a narrative performed. Programmed regulation its pathways implicated periodontal infection were reviewed. Results Multicellular organisms dispose unnecessary or damaged cells via death. lies at core balance survival pathological progress infection. Periodontitis is complex infectious disease involving virulence factors pathogens tightly regulated immune responses host. Different types can play opposite periodontitis exert action combinatorially. Conclusion The coordinated system extensive crosstalk among them fundamental role pathophysiology Illuminating precise mechanisms could open up novel therapeutic approaches.

Language: Английский

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Hyperuricemia Exacerbates Experimental Periodontitis via Uric Acid‐Induced Periodontal Inflammation and Oxidative Stress

Journal Of Clinical Periodontology, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 20, 2025

ABSTRACT Aim To investigate the effects of hyperuricemia on periodontitis and underlying mechanisms by establishing combined animal cell models. Methods A mouse model was established potassium oxonate injection, with sodium carboxymethylcellulose treatment serving as controls. Both models were treated or without induction ( n = 10/group). RAW264.7 macrophages THP‐1‐derived stimulated Porphyromonas gingivalis ‐lipopolysaccharide in presence normal excessive concentrations uric acid. Allopurinol intervention applied to both Periodontal destruction measured micro‐computed tomography histology. The immune response oxidative stress periodontium assessed using various methods including immunohistochemistry, quantitative PCR, western blotting, flow cytometry multiplex cytokine assays. Results Potassium successfully induced affecting serum glucose/lipid levels xanthine oxidoreductase activity. In mice periodontitis, exacerbated alveolar bone loss osteoclasts M1 macrophages. Mechanistically, promoted NLRP3 inflammasome activation, disrupted inflammatory vitro. reversed all relevant changes Conclusion Hyperuricemia exacerbates possibly via acid‐induced periodontal inflammation stress.

Language: Английский

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Micro-/nano-structured zirconia surface promotes osteogenic differentiation of human bone marrow mesenchymal stem cells by reducing pyroptosis under inflammatory conditions

Journal of Dental Sciences, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 1, 2025

Language: Английский

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Circadian disruption by simulated shift work aggravates periodontitis via orchestrating BMAL1 and GSDMD-mediated pyroptosis

International Journal of Oral Science, Journal Year: 2025, Volume and Issue: 17(1)

Published: Feb. 25, 2025

Abstract Approximately 20% to 30% of the global workforce is engaged in shift work. As a significant cause circadian disruption, work closely associated with an increased risk for periodontitis. Nevertheless, how work-related disruption functions periodontitis remains unknown. Herein, we employed simulated model constructed by controlling environmental light-dark cycles and revealed that exacerbated progression experimental RNA sequencing vitro experiments indicated downregulation core protein brain muscle ARNT-like 1 (BMAL1) activation Gasdermin D (GSDMD)-mediated pyroptosis were involved pathogenesis that. Mechanically, BMAL1 regulated GSDMD-mediated suppressing NOD-like receptor 3 (NLRP3) inflammasome signaling through modulating nuclear subfamily group member (NR1D1), inhibiting Gsdmd transcription via directly binding E-box elements its promoter. accelerated progression, whereas downregulated under further aggravated periodontal destruction increasing GSDMD activity. And restoring level recovery SR8278 injection alleviated work-exacerbated lessening pyroptosis. These findings provide new evidence potential interventional targets disruption-accelerated

Language: Английский

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