The Role of Gingival Fibroblasts in the Pathogenesis of Periodontitis

Journal of Dental Research, Год журнала: 2023, Номер 102(5), С. 489 - 496

Опубликована: Март 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.

Язык: Английский

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

Journal Of Clinical Periodontology, Год журнала: 2025, Номер unknown

Опубликована: Фев. 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.

Язык: Английский

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

Small Structures, Год журнала: 2024, Номер 5(3)

Опубликована: Фев. 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.

Язык: Английский

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

Scientific Reports, Год журнала: 2025, Номер 15(1)

Опубликована: Янв. 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.

Язык: 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, Год журнала: 2025, Номер unknown

Опубликована: Фев. 1, 2025

Язык: 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, Год журнала: 2023, Номер 373, С. 114658 - 114658

Опубликована: Дек. 21, 2023

Язык: Английский

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Insight into the role of macrophages in periodontitis restoration and development

Virulence, Год журнала: 2024, Номер 15(1)

Опубликована: Ноя. 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

Язык: Английский

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

Molecular Medicine Reports, Год журнала: 2023, Номер 28(5)

Опубликована: Сен. 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.

Язык: Английский

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Exploring the molecular mechanisms of ferroptosis-related genes in periodontitis: a multi-dataset analysis

BMC Oral Health, Год журнала: 2024, Номер 24(1)

Опубликована: Май 27, 2024

Abstract Purpose This study aims to elucidate the biological functions of ferroptosis-related genes in periodontitis, along with their correlation tumor microenvironment (TME) features such as immune infiltration. It provide potential diagnostic markers ferroptosis for clinical management periodontitis. Methods Utilizing periodontitis-related microarray dataset GSE16134 from Gene Expression Omnibus (GEO) and a set 528 identified prior studies, this research unveils differentially expressed Subsequently, protein–protein interaction network was constructed. Subtyping periodontitis explored, followed by validation through cell infiltration gene enrichment analyses. Two algorithms, randomForest SVM(Support Vector Machine), were employed reveal The efficacy, correlation, transcriptional regulatory networks these further assessed. Finally, targeted drugs predicted. Results A total 36 (30 upregulated, 6 downregulated) 829 between 9 samples control group. Subsequent machine learning algorithm screening highlighted 4 key genes: SLC1A5(Solute Carrier Family 1 Member 5), SLC2A14(Solute 14), LURAP1L(Leucine Rich Adaptor Protein Like), HERPUD1(Homocysteine Inducible ER With Ubiquitin Like Domain 1). Exploration genes, supported time-correlated ROC analysis, demonstrated reliability, while results indicated strong factors. Furthermore, Set Enrichment Analysis (GSEA) conducted four revealing GO/KEGG pathways that have significant impact on predicted associated Conclusions study, including SLC1A5, SLC2A14, LURAP1L, HERPUD1, may serve novel therapeutic targets They are likely involved occurrence development mechanisms infiltration, cellular metabolism, inflammatory chemotaxis, potentially linking pathway progression Targeted flurofamide, L-733060, memantine, tetrabenazine, WAY-213613 hold promise interventions genes.

Язык: Английский

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Could the periodontal therapy improve the cardiologic patient health? A narrative review

Current Problems in Cardiology, Год журнала: 2024, Номер 49(9), С. 102699 - 102699

Опубликована: Июнь 7, 2024

Cardiovascular diseases (CVD) is the major cause of mortality globally, with increasing evidence suggesting a link between periodontitis, and CVD. This study aims to explore association periodontitis CVD, impact periodontal therapy on cardiovascular health. review synthesized findings from preclinical clinical studies, without publication year restrictions, examining CVD through various lenses. Scientific databases were inspected keywords related The identifies substantial an increased risk several supported by both epidemiological interventional studies. Results suggest complexity relationship, influenced factors like severity presence other systemic conditions. Clinical data indicates that therapy, particularly non-surgical may reduce inflammatory markers thus play role in primary secondary prevention events, highlighting potential not only maintain oral health but also modulate factors. Current supports significant risk, promoting integrated healthcare approaches consider as key-component care wellbeing.

Язык: Английский

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