EZH2 Regulates Lipopolysaccharide-Induced Periodontal Ligament Stem Cell Proliferation and Osteogenesis through TLR4/MyD88/NF-κB Pathway

Wang, Pengcheng; Tian, Hui; Zhang, Zheng; Wang, Zuomin

doi:10.1155/2021/7625134

Cited by 21 publications

(22 citation statements)

References 38 publications

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“…We demonstrated that GMSC-Exo attenuated LPS-induced inflammatory responses by suppressing the expression of NF-κB and Wnt5a in PDLSCs. Emerging evidence has shown that LPS derived from E. coli affects the osteogenesis of PDLSCs and human dental pulp stem cells through the toll-like receptor 4 (TLR4)-mediated NF-κB pathway and Wnt5a ( Li et al, 2014 ; He et al, 2014 ; P.; Wang et al, 2021 ). Čebatariūnienė et al (2019) determined that exosomes from PDLSCs could suppress NF-κB signaling, while combined treatment with exosomes and anti-TLR4 blocking antibodies attenuated the inhibitory effect on the NF-κB activity, indicating that the effect might be achieved via competition for TLR4.…”

Section: Discussionmentioning

confidence: 99%

Exosomes Derived From Human Gingival Mesenchymal Stem Cells Attenuate the Inflammatory Response in Periodontal Ligament Stem Cells

Sun

Wang

Liu³

et al. 2022

Front. Chem.

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This study aimed to explore the effects of exosomes derived from human gingival mesenchymal stem cells (GMSC-Exo) on the inflammatory response of periodontal ligament stem cells (PDLSCs) in an inflammatory microenvironment in order to restore the regenerative potential of PDLSCs, which promotes periodontal tissue regeneration in patients with periodontitis. Periodontitis is a chronic infectious disease characterized by periodontal tissue inflammation and alveolar bone destruction. PDLSCs are regarded as promising seed cells for restoring periodontal tissue defects because of their ability to regenerate cementum/PDL-like tissue and alveolar bone. However, PDLSCs in the inflammatory environment show significantly attenuated regenerative potential. GMSC-Exo have been reported to have anti-inflammatory and immunosuppressive properties. In this study, we investigated the effects of GMSC-Exo on the inflammatory response of PDLSCs induced by lipopolysaccharides (LPS). LPS was used to simulate the inflammatory microenvironment of periodontitis in vitro. GMSC-Exo were extracted from the culture supernatant of GMSCs by ultracentrifugation. We found that GMSC-Exo attenuated the inflammatory response of PDLSCs induced by LPS. Furthermore, compared to treatment with LPS, treatment with GMSC-Exo attenuated the expression of NF-κB signaling and Wnt5a in LPS-induced PDLSCs. In conclusion, we confirmed that GMSC-Exo could suppress the inflammatory response of PDLSCs by regulating the expression of NF-κB signaling and Wnt5a, which paves the way for the establishment of a therapeutic approach for periodontitis.

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Section: Discussionmentioning

confidence: 99%

Exosomes Derived From Human Gingival Mesenchymal Stem Cells Attenuate the Inflammatory Response in Periodontal Ligament Stem Cells

Sun

Wang

Liu³

et al. 2022

Front. Chem.

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“…Up to date, numerous studies have revealed several signaling pathways involved in the development of periodontitis, such as NF- κ B signaling pathway [ 15 ], IL-17 signaling pathway [ 16 ], and Wnt/ β -catenin signaling pathway [ 17 ]. Our previous study has shown that NF- κ B signaling is involved in periodontal ligament stem cells osteogenesis following inflammatory stimulation [ 18 ]. IL-17 signaling pathway is related to the metabolism of the alveolar bone [ 16 ].…”

Section: Discussionmentioning

confidence: 99%

Identification of Key Genes and Pathways Associated with Oxidative Stress in Periodontitis

Zhang

Zheng

Bian

et al. 2022

Oxidative Medicine and Cellular Longevity

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Background and Objective. Oxidative stress has been associated with the progression of periodontitis. However, oxidative stress-related genes (OS-genes) have not been used as disease-specific biomarkers that correlate with periodontitis progression. This study is aimed at screening the key OS-genes and pathways in periodontitis by bioinformatics methods. Methods. The differentially expressed genes (DEGs) were identified using periodontitis-related microarray from the GEO database, and OS-genes were extracted from GeneCards database. The intersection of the OS-genes and the DEGs was considered as oxidative stress-related DEGs (OS-DEGs) in periodontitis. The Pearson correlation and protein-protein interaction analyses were used to screen key OS-genes. Gene set enrichment, functional enrichment, and pathway enrichment analyses were performed in OS-genes. Based on key OS-genes, a risk score model was constructed through logistic regression, receiver operating characteristic curve, and stratified analyses. Results. In total, 74 OS-DEGs were found in periodontitis, including 65 upregulated genes and 9 downregulated genes. Six of them were identified as key OS-genes (CXCR4, SELL, FCGR3B, FCGR2B, PECAM1, and ITGAL) in periodontitis. All the key OS-genes were significantly upregulated and associated with the increased risk of periodontitis. Functional enrichment analysis showed that these genes were mainly associated with leukocyte cell-cell adhesion, phagocytosis, and cellular extravasation. Pathway analysis revealed that these genes were involved in several signaling pathways, such as leukocyte transendothelial migration and osteoclast differentiation. Conclusion. In this study, we screened six key OS-genes that were screened as risk factors of periodontitis. We also identified multiple signaling pathways that might play crucial roles in regulating oxidative stress damage in periodontitis. In the future, more experiments need to be carried out to validate our current findings.

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“…TLR4 recognizes DAMPs [ 13 ], which are associated with host cell components released after cell damage [ 5 , 14 , 15 ]. We revealed that levels of certain DAMPs, including HMGB1, S100A8, and S100A9, were elevated after blood mixing, and this finding was corroborated by other reports [ 16 , 17 , 18 , 19 , 20 ] on blood transfusions ( Figure 3 ).…”

Section: Discussionmentioning

confidence: 99%

“…TLR4 ligands recognize DAMPs and pathogen-associated molecular patterns (PAMPs) [ 5 , 14 , 15 , 23 ], such as circulating LPS (endotoxin). PAMPs are associated with microbial pathogens [ 24 ].…”

Section: Discussionmentioning

confidence: 99%

“…PAMP signaling is unlikely to participate proinflammatory cytokine release signaling pathway for the following two reasons: First, during blood mixing, PAMPs such as circulating LPS from microbial pathogens were not considered because no patients had a pathogenic infection. Second, after blood mixing, the levels of LPS-binding protein, which binds to PAMPs but not DAMPs, were not increased, as shown in Figure 4 [ 14 , 15 ]. Therefore, blood mixing may initiate platelet TLR4 expression, which could trigger an innate immune system response that is likely independent of PAMPs.…”

Section: Discussionmentioning

confidence: 99%

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Platelet Toll-like Receptor 4–Related Innate Immunity Potentially Participates in Transfusion Reactions Independent of ABO Compatibility: An Ex Vivo Study

Tsai

Hsu

et al. 2021

Biomedicines

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The role of platelet TLR4 in transfusion reactions remains unclear. This study analyzed platelet TLR4 and certain damage-associated molecular patterns (DAMPs) and evaluated how ABO compatibility affected TLR4 expression after a simulated ex vivo transfusion. A blood bank was the source of donor red blood cells. Blood from patients undergoing cardiac surgery was processed to generate a washed platelet suspension to which the donor blood was added in concentrations 1, 5, and 10% (v/v). Blood-mixing experiments were performed on four groups: a 0.9% saline control group (n = 31); a matched-blood-type mixing group (group M, n = 20); an uncross-matched ABO-specific mixing group (group S, n = 20); and an ABO-incompatible blood mixing group (group I, n = 20). TLR4 expression in the platelets was determined after blood mixing. We evaluated levels of TLR4-binding DAMPs (HMGB1, S100A8, S100A9, and SAA), lipopolysaccharide-binding protein, and endpoint proteins in the TLR4 signaling pathway. In the M, S, and I groups, 1, 5, and 10% blood mixtures significantly increased TLR4 expression (all p < 0.001) in a concentration-dependent manner. Groups M, S, and I were not discovered to have significantly differing TLR4 expression (p = 0.148). HMGB1, S100A8, and S100A9 levels were elevated in response to blood mixing, but SAA, lipopolysaccharide-binding protein, TNF-α, IL-1β, and IL-6 levels were not. Blood mixing may elicit innate immune responses by upregulating platelet TLR4 and DAMPs unassociated with ABO compatibility, suggesting that innate immunity through TLR4-mediated signaling may induce transfusion reactions.

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EZH2 Regulates Lipopolysaccharide-Induced Periodontal Ligament Stem Cell Proliferation and Osteogenesis through TLR4/MyD88/NF-κB Pathway

Cited by 21 publications

References 38 publications

Exosomes Derived From Human Gingival Mesenchymal Stem Cells Attenuate the Inflammatory Response in Periodontal Ligament Stem Cells

Exosomes Derived From Human Gingival Mesenchymal Stem Cells Attenuate the Inflammatory Response in Periodontal Ligament Stem Cells

Identification of Key Genes and Pathways Associated with Oxidative Stress in Periodontitis

Platelet Toll-like Receptor 4–Related Innate Immunity Potentially Participates in Transfusion Reactions Independent of ABO Compatibility: An Ex Vivo Study

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