The role of PHF8 and TLR4 in osteogenic differentiation of periodontal ligament cells in inflammatory environment

Liu, Zhao; He, Yiheng; Xu, Chenrong; Li, Jianjia; Zeng, Su; Yang, Xi; Han, Qianqian

doi:10.1002/jper.20-0285

Cited by 18 publications

(15 citation statements)

References 33 publications

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“…Researchers have revealed that TLR4 can be activated by LPS to regulate NF-κB pathway of PDLSCs to subsequently decrease their osteogenic potential ( Li et al, 2014 ). Recently, it was reported that the upregulation of TLR4 inhibits the osteogenic differentiation of PDLSCs in an inflammatory environment, suggesting the important role of TLR4 for regenerative capacity of PDLSCs in periodontitis ( Liu et al, 2020 ). However, the specific regulatory mechanism needs to be further studied.…”

Section: Introductionmentioning

confidence: 99%

CircMAP3K11 Contributes to Proliferation, Apoptosis and Migration of Human Periodontal Ligament Stem Cells in Inflammatory Microenvironment by Regulating TLR4 via miR-511 Sponging

et al. 2021

Front. Pharmacol.

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Growing number of studies regarding the role of circRNAs in the development of various diseases have emerged in recent years, but the role of circRNAs in periodontitis pathogenesis remains obscure. Human periodontal ligament stem cells (hPDLSCs) play a critical role in periodontal remodeling, regeneration and repair processes, and their regenerative capacity could be prohibited in local periodontal inflammatory microenvironment. Herein, we sought to uncover the molecular mechanisms of periodontitis pathogenesis by investigating the role of circMAP3K11 (hsa_circ_002284) for regenerative capacity of hPDLSCs under an inflammatory condition. The hPDLSCs isolated from periodontitis patients were used as a cell model of inflammatory microenvironment to study the effect of the circMAP3K11/miR-511-3p/TLR4 axis on the proliferation, apoptosis and migration of hPDLSCs under inflammatory conditions. Compared to the periodontal tissues from normal subjects, those from periodontitis patients exhibited higher expression levels of circMAP3K11 and TLR4, and lower expression level of miR-511-3p. Both the expressions of circMAP3K11 and TLR4 were negatively correlated with the expressions of miR-511-3p in periodontitis. In vitro studies demonstrated that circMAP3K11 is capable of enhancing hPDLSCs proliferation and migration, and reducing the apoptosis of hPDLSCs. We also found that circMAP3K11 could up-regulate the expression of transcription factors that are closely related to periodontal regeneration (Runx2, OSX, ATF4, and BSP). RT-PCR and western blot showed that the inhibitory role of miR-511-3p on TLR4 expression could be reversed by circMAP3K11, which was in line with the results of bioinformatics tools and luciferase reporter assay. Meanwhile, both in vitro and in vivo studies indicated that circMAP3K11 could reverse the effects of miR-511-3p in periodontitis, which further confirmed that circMAP3K11 functioned as a ‘sponge’ of miR-511-3p to positively regulate the expression of TLR4. Taken together, our study preliminarily uncovered a circMAP3K11/miR-511-3p/TLR4 axis that regulates the function of hPDLSCs in periodontitis, providing novel insight and scientific base in the treatment of periodontal tissue regeneration based on stem cells.

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Section: Introductionmentioning

confidence: 99%

CircMAP3K11 Contributes to Proliferation, Apoptosis and Migration of Human Periodontal Ligament Stem Cells in Inflammatory Microenvironment by Regulating TLR4 via miR-511 Sponging

et al. 2021

Front. Pharmacol.

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“…EVs treatment effectively suppressed TLR4 transcription, which was weakened by downregulation of miR-590-3p. Upregulation of TLR4 represses the osteogenesis of PDLSCs in inflammatory environment, implying the vital functionality of TLR4 in the regenerative capacity of PDLSCs in periodontitis [Liu et al, 2020c]. Briefly, our results demonstrated that miR-590-3p targeted TLR4.…”

Section: Discussionmentioning

confidence: 51%

Effect of Human Periodontal Ligament Stem Cell-Derived Extracellular Vesicles on Macrophage Pyroptosis and Periodontal Inflammatory Injury in Periodontitis

Han

Chen

2021

Cells Tissues Organs

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Periodontitis is an inflammatory disease resulting from subgingival microorganisms. Human periodontal ligament stem cells (hPDLSCs) can be applied in periodontal tissue regeneration. This study investigated the effect of hPDLSC-derived extracellular vesicles (EVs) on periodontitis. hPDLSC-derived EVs were isolated and identified. The murine model of periodontitis was established by ligation, and the cell model of periodontitis was established by treatment of macrophages with lipopolysaccharide (LPS). The effects of EVs on macrophage pyroptosis and periodontal inflammatory injury were measured by the means of HE staining, detection of LDH content, CCK-8 assay, Calcein-AM/PI staining, ELISA, Western blot, as well as measurement of caspase-1, SOD, and MDA. miR-590-3p expression was detected using RT-qPCR. miR-590-3p expression was then intervened to validate the effect of miR-590-3p on macrophage pyroptosis. The binding relationship between miR-590-3p and TLR4 was verified using dual-luciferase assay. Functional rescue experiment was performed to validate the role of TLR4 in macrophage pyroptosis. The results showed that inflammatory levels and macrophage pyroptosis were enhanced in the in vivo and in vitro models of periodontitis, evidenced by the increased NLRP3, GSDMD-N, caspase-1, IL-1β, IL-18, TNF-α, and MDA and decreased IL-10 and SOD. EVs alleviated periodontal inflammatory injury and macrophage pyroptosis. Physiologically, EVs carried miR-590-3p into macrophages to upregulate miR-590-3p expression and thereby suppress TLR4 transcription. miR-590-3p silencing or TLR4 overexpression reduced the inhibitory effect of EVs on macrophage pyroptosis. Collectively, EVs carried miR-590-3p into macrophages to subsequently inhibit TLR4 transcription, thereby reducing macrophage pyroptosis and alleviating periodontal inflammatory injury.

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“…This review identified ten relevant studies analysing post-translational histone modifications implicated in chronic periodontitis, and seven relevant studies focusing on HDACi for treating periodontitis. Of these studies, there was only one cross-sectional study [ 45 ], two in vivo studies [ 46 , 47 ], and the remaining publications were in vitro [ 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 ]. All publications in Table 2 and Table 3 were critically assessed to explore correlations between histone modification and the periodontal inflammatory response, along with the effects of various novel HDACi on human in vitro cells.…”

Section: Resultsmentioning

confidence: 99%

The Relevance of DNA Methylation and Histone Modification in Periodontitis: A Scoping Review

Liaw

Liu

Ivanovski

et al. 2022

Cells

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Background: Periodontitis is a chronic inflammatory disease involving an interplay between bacteria, inflammation, host response genes, and environmental factors. The manifestation of epigenetic factors during periodontitis pathogenesis and periodontal inflammation is still not well understood, with limited reviews on histone modification with periodontitis management. This scoping review aims to evaluate current evidence of global and specific DNA methylation and histone modification in periodontitis and discuss the gaps and implications for future research and clinical practice. Methods: A scoping literature search of three electronic databases was performed in SCOPUS, MEDLINE (PubMed) and EMBASE. As epigenetics in periodontitis is an emerging research field, a scoping review was conducted to identify the extent of studies available and describe the overall context and applicability of these results. Results: Overall, 30 studies were evaluated, and the findings confirmed that epigenetic changes in periodontitis comprise specific modifications to DNA methylation patterns and histone proteins modification, which can either dampen or promote the inflammatory response to bacterial challenge. Conclusions: The plasticity of epigenetic modifications has implications for the future development of targeted epi-drugs and diagnostic tools in periodontitis. Such advances could be invaluable for the early detection and monitoring of susceptible individuals.

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The role of PHF8 and TLR4 in osteogenic differentiation of periodontal ligament cells in inflammatory environment

Cited by 18 publications

References 33 publications

CircMAP3K11 Contributes to Proliferation, Apoptosis and Migration of Human Periodontal Ligament Stem Cells in Inflammatory Microenvironment by Regulating TLR4 via miR-511 Sponging

CircMAP3K11 Contributes to Proliferation, Apoptosis and Migration of Human Periodontal Ligament Stem Cells in Inflammatory Microenvironment by Regulating TLR4 via miR-511 Sponging

Effect of Human Periodontal Ligament Stem Cell-Derived Extracellular Vesicles on Macrophage Pyroptosis and Periodontal Inflammatory Injury in Periodontitis

The Relevance of DNA Methylation and Histone Modification in Periodontitis: A Scoping Review

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