Osteoclastogenesis in Periodontitis: Signaling Pathway, Synthetic and Natural Inhibitors

Ketherin, Ketherin; Sandra, Ferry

doi:10.21705/mcbs.v2i1.16

Cited by 8 publications

(9 citation statements)

References 56 publications

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“…Further, inhibition of p38 may particularly have potential therapeutic value in limiting periodontitis progression at multiple levels of the immune response via its effects on different extracellular stimuli (Kirkwood and Rossa, 2009). Of note, bone resorption, a hallmark of periodontitis, is mainly affected through RANKL, a vital osteoclast differentiation factor (Taubman et al, 2005) and Tumor Necrosis Factor (TNF)-a, majorly activated by MAPK and NF-κB pathways (Ketherin and Sandra, 2018), indicating a key role of these pathways in osteoimmunology.…”

Section: Discussionmentioning

confidence: 99%

Deep Learning Reveals Key Immunosuppression Genes and Distinct Immunotypes in Periodontitis

et al. 2021

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BackgroundPeriodontitis is a chronic immuno-inflammatory disease characterized by inflammatory destruction of tooth-supporting tissues. Its pathogenesis involves a dysregulated local host immune response that is ineffective in combating microbial challenges. An integrated investigation of genes involved in mediating immune response suppression in periodontitis, based on multiple studies, can reveal genes pivotal to periodontitis pathogenesis. Here, we aimed to apply a deep learning (DL)-based autoencoder (AE) for predicting immunosuppression genes involved in periodontitis by integrating multiples omics datasets.MethodsTwo periodontitis-related GEO transcriptomic datasets (GSE16134 and GSE10334) and immunosuppression genes identified from DisGeNET and HisgAtlas were included. Immunosuppression genes related to periodontitis in GSE16134 were used as input to build an AE, to identify the top disease-representative immunosuppression gene features. Using K-means clustering and ANOVA, immune subtype labels were assigned to disease samples and a support vector machine (SVM) classifier was constructed. This classifier was applied to a validation set (Immunosuppression genes related to periodontitis in GSE10334) for predicting sample labels, evaluating the accuracy of the AE. In addition, differentially expressed genes (DEGs), signaling pathways, and transcription factors (TFs) involved in immunosuppression and periodontitis were determined with an array of bioinformatics analysis. Shared DEGs common to DEGs differentiating periodontitis from controls and those differentiating the immune subtypes were considered as the key immunosuppression genes in periodontitis.ResultsWe produced representative molecular features and identified two immune subtypes in periodontitis using an AE. Two subtypes were also predicted in the validation set with the SVM classifier. Three “master” immunosuppression genes, PECAM1, FCGR3A, and FOS were identified as candidates pivotal to immunosuppressive mechanisms in periodontitis. Six transcription factors, NFKB1, FOS, JUN, HIF1A, STAT5B, and STAT4, were identified as central to the TFs-DEGs interaction network. The two immune subtypes were distinct in terms of their regulating pathways.ConclusionThis study applied a DL-based AE for the first time to identify immune subtypes of periodontitis and pivotal immunosuppression genes that discriminated periodontitis from the healthy. Key signaling pathways and TF-target DEGs that putatively mediate immune suppression in periodontitis were identified. PECAM1, FCGR3A, and FOS emerged as high-value biomarkers and candidate therapeutic targets for periodontitis.

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Section: Discussionmentioning

confidence: 99%

Deep Learning Reveals Key Immunosuppression Genes and Distinct Immunotypes in Periodontitis

et al. 2021

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“…25,27 IL-6, which produced by the influence of LPS, IL-1β and TNF-α, also causes bone resorption and enhances the synthesis of PGE2, acute phase proteins, and chemokines. 1,[28][29][30][31][32] IL-6 generates oxidative stress and may lead to a short-term aggregation of H 2 O 2 in mitochondria, resulting in damage of mitochondrial. 33 IL-6 also affects the invasion and metastasis process by promoting MMPs expressions.…”

Section: Stimulation Of Chronic Inflammationmentioning

confidence: 99%

Microbiome in Oral Squamous Cell Carcinoma: Mechanisms and Signaling Pathways

Hayati¹,

Panjaitan²,

Sandra³

2020

Mol Cell Biomed Sci

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Oral squamous cell carcinoma is part of head and neck squamous cell carcinoma which is the ultimate cause of morbidity and mortality in cancer. The alteration of microbial community in the saliva might act as a helpful marker for the prediction, detection and prognosis oral cancer, particularly the transition of cancer precursor lesion. There are three mechanisms of action of oral microbiota in cancer pathogenesis, chronic inflammation of bacterial stimulation, carcinogenesis by cytoskeletal rearrangements, and carcinogenic substances that produced by microorganisms. Changes in the composition of microbiota could therefore have the potential to be used as a significant oral biomarker to predict the pathological transition from oral epithelial precursor lesion to cancer.Keywords: microbiome, oral cancer cellular proliferation, microorganism, oral cancer, oral squamous cell carcinoma

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“…Ethanolic extract of various herbs, such as those extracted from Cosmos caudatus, mangosteen pericarp, and Piperomia pellucida L., has been reported to affect inflammatory cytokine also play a role as natural antioxidant in inflammation pathway. (16,17) CAPE, is an ethanolic extract of propolis, has been shown to have anti-apoptotic effects and antioxidants. (12) In the previous study, the benefit of ethanolic extract was proved to prevent skin manifestations and tissue necrosis in anthrax rats model.…”

Section: Introductionmentioning

confidence: 99%

Indonesian Propolis Inhibit Proinflammatory Cytokines, Apoptosis and Oxidative Stress in Anthrax Animal Model

Dewi¹,

Redhono²,

Susanto³

et al. 2022

Indones Biomed J

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BACKGROUND: Anthrax is a zoonotic disease caused by Bacillus anthracis, whose endospores stimulate the release of pro-inflammatory cytokines and promote oxidative stress. Propolis, a natural resource that can be found in Indonesia, has been proven to have anti-apoptotic and antioxidant role which might be a potential adjuvant therapy for anthrax treatment. Hence in this study we aimed to investigate effect of propolis as an anti-inflammatory, anti-apoptotic, and antioxidant in anthrax rats model by examining the level of tumor necrosis factor (TNF)-α, caspase-3, and malondialdehyde (MDA), respectively.METHODS: This was an experimental post-test only study with 40 male rats weighed 180-200 g that were induced by anthrax spores injected subcutaneously. The rats were divided into one control positive group and four intervention groups that were administered with 200 mg/kgBW propolis extract for 7 to 14 days. The levels of serum TNF-α, caspase-3, and MDA were measured using enzyme-linked immunosorbent assay (ELISA) and analyzed with bivariate analysis.RESULTS: TNF-α, caspase-3, and MDA level were found lower in anthrax rats model given ethanol extract of propolis than the control group. The lowest concentration of TNF-α value was found in group administered with propolis extract 200 mg/kgBW for 7 days before the anthrax induction (6.136±0.205 pg/mL). The results were similar to the MDA serum and caspase-3 which were the lowest when the propolis was administered 7 days earlier (1.893±0.188 nmol/mL and 2.040±0.067 ng/mL). There was significant difference in the TNF-α, caspase-3, and MDA serum levels (p≤0.001) compared to control group.CONCLUSION: Propolis has anti-apoptotic and antioxidant effects which can be used as complementary therapy in anthrax infection.KEYWORDS: propolis, anthrax, anti-apoptotic, antioxidants

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Osteoclastogenesis in Periodontitis: Signaling Pathway, Synthetic and Natural Inhibitors

Cited by 8 publications

References 56 publications

Deep Learning Reveals Key Immunosuppression Genes and Distinct Immunotypes in Periodontitis

Deep Learning Reveals Key Immunosuppression Genes and Distinct Immunotypes in Periodontitis

Microbiome in Oral Squamous Cell Carcinoma: Mechanisms and Signaling Pathways

Indonesian Propolis Inhibit Proinflammatory Cytokines, Apoptosis and Oxidative Stress in Anthrax Animal Model

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