scholarly journals Inhibition of Tet1- and Tet2-mediated DNA demethylation promotes immunomodulation of periodontal ligament stem cells

2019 ◽  
Vol 10 (10) ◽  
Author(s):  
Tingting Yu ◽  
Dawei Liu ◽  
Ting Zhang ◽  
Yanheng Zhou ◽  
Songtao Shi ◽  
...  
Keyword(s):  
Stem Cells ◽  
Periodontal Ligament ◽  
Fas Ligand ◽  
Immune Therapy ◽  
Wnt Signaling Pathway ◽  
Dna Demethylation ◽  
Periodontal Ligament Stem Cells ◽  
Promising Target ◽  
Immunomodulatory Properties ◽  
Underlying Mechanisms

Abstract Periodontal ligament stem cells (PDLSCs) possess great potential for clinical treatment of immune diseases due to their extensive immunomodulatory properties. However, the underlying mechanisms that govern the immunomodulatory properties of mesenchymal stem cells (MSCs) are still not fully elucidated. Here, we show that member of the Ten-eleven translocation (Tet) family, a group of DNA demethylases, are capable of regulating PDLSC immunomodulatory functions. Tet1 and Tet2 deficiency enhance PDLSC-induced T cell apoptosis and ameliorate the disease phenotype in colitis mice. Mechanistically, we found that downregulation of Tet1 and Tet2 leads to hypermethylation of DKK-1 promoter, leading to the activation of WNT signaling pathway and therefore promoting Fas ligand (FasL) expression, which results in elevated immunomodulatory capacity of PDLSCs. These results reveal a previously unrecognized role of Tet1 and Tet2 in regulating immunomodulation of PDLSCs. This Tet/DKK-1/FasL cascade may serve as a promising target for enhancing PDLSC-based immune therapy.

scholarly journals Periodontal ligament stem cells regulate apoptosis of neutrophils

Open Medicine ◽  
2017 ◽  
Vol 12 (1) ◽  
pp. 19-23 ◽  
Author(s):  
Qing Wang ◽  
Gang Ding ◽  
Xin Xu
Keyword(s):  
Stem Cells ◽  
Periodontal Ligament ◽  
Neutralizing Antibody ◽  
Cell Contact ◽  
Neutrophil Apoptosis ◽  
Periodontal Ligament Stem Cells ◽  
Cell Based Therapy ◽  
Transwell Culture ◽  
Underlying Mechanisms ◽  
Cell Cell

AbstractPeriodontal ligament stem cells (PDLSCs) are promising cell resource for the cell-based therapy for periodontitis and regeneration of bio-root. In this study, we investigated the effect of PDLSCs on neutrophil, a critical constituent of innate immunity, and the underlying mechanisms. The effect of PDLSCs on the proliferation and apoptosis of resting neutrophils and IL-8 activated neutrophils was tested under cell-cell contact culture and Transwell culture, with or without anti-IL-6 neutralizing antibody. We found that PDLSCs could promote the proliferation and reduce the apoptosis of neutrophils whether under cell-cell contact or Transwell culture. Anti-IL-6 antibody reduced PDLSCs-mediated inhibition of neutrophil apoptosis. IL-6 at the concentration of 10ng/ml and 20ng/ml could inhibit neutrophil apoptosis statistically. Collectively, PDLSCs could reduce the apoptosis of neutrophils via IL-6.

Immunomodulatory properties of human periodontal ligament stem cells

2009 ◽  
Vol 219 (3) ◽  
pp. 667-676 ◽  
Author(s):  
Naohisa Wada ◽  
Danijela Menicanin ◽  
Songtao Shi ◽  
P. Mark Bartold ◽  
Stan Gronthos
Keyword(s):  
Stem Cells ◽  
Periodontal Ligament ◽  
Periodontal Ligament Stem Cells ◽  
Immunomodulatory Properties

scholarly journals Guanylate-Binding Protein 1 Promotes Migration and Invasion of Human Periodontal Ligament Stem Cells

2018 ◽  
Vol 2018 ◽  
pp. 1-8 ◽  
Author(s):  
Shi Bai ◽  
Tao Chen ◽  
Xia Deng
Keyword(s):  
Stem Cells ◽  
Periodontal Ligament ◽  
Binding Protein ◽  
Ectopic Expression ◽  
Migration And Invasion ◽  
Dependent Manner ◽  
Periodontal Ligament Stem Cells ◽  
Underlying Mechanisms ◽  
Guanylate Binding Protein

Mesenchymal stem/stromal cells (MSCs) are capable of migrating to sites of injury and inflammation in response to various cytokines to improve tissue repair. Previous studies have shown interferon-gamma (IFN-γ) promoted migration of the V54/2 cell line and dental pulp stem cells (DPSCs), but the underlying mechanisms remain largely unknown. In this study, we found IFN-γ induced migration and invasion of periodontal ligament stem cells (PDLSCs) in a dose-dependent manner in vitro. While knockdown of guanylate-binding protein 1 (GBP1) suppressed IFN-γ-induced migration and invasion, ectopic expression of GBP1 potentiated IFN-γ-induced migration and invasion of PDLSCs. Furthermore, we demonstrated GBP1 was required for IFN-γ-induced processing of matrix metallopeptidase 2 (MMP2) in PDLSCs. Our findings indicate that GBP1 promotes IFN-γ-induced migration and invasion of PDLSCs by MMP2, and GBP1 may serve as a new target to facilitate MSC homing and migration.

The Immunomodulatory Properties of Periodontal Ligament Stem Cells Isolated from Inflamed Periodontal Granulation

2014 ◽  
Vol 199 (4) ◽  
pp. 256-265 ◽  
Author(s):  
Chenghua Li ◽  
Xinwen Wang ◽  
Jun Tan ◽  
Tao Wang ◽  
Qintao Wang
Keyword(s):  
Stem Cells ◽  
Periodontal Ligament ◽  
Periodontal Ligament Stem Cells ◽  
Immunomodulatory Properties

scholarly journals 3D Clumps/Extracellular Matrix Complexes of Periodontal Ligament Stem Cells Ameliorate the Attenuating Effects of LPS on Proliferation and Osteogenic Potential

2021 ◽  
Vol 11 (6) ◽  
pp. 528
Author(s):  
Spoorthi Ravi Banavar ◽  
Swati Yeshwant Rawal ◽  
Shaju Jacob Pulikkotil ◽  
Umer Daood ◽  
Ian C. Paterson ◽  
...  
Keyword(s):  
Stem Cells ◽  
Periodontal Ligament ◽  
3D Culture ◽  
Osteogenic Potential ◽  
Culture Methods ◽  
Periodontal Ligament Stem Cells ◽  
Raman Analysis ◽  
Atp Production ◽  
Tnf Α ◽  
Inflammatory Milieu

Background: The effects of lipopolysaccharide (LPS) on cell proliferation and osteogenic potential (OP) of MSCs have been frequently studied. Objective: to compare the effects of LPS on periodontal-ligament-derived mesenchymal stem cells (PDLSCs) in monolayer and 3D culture. Methods: The PDLSCs were colorimetrically assessed for proliferation and osteogenic potential (OP) after LPS treatment. The 3D cells were manually prepared by scratching and allowing them to clump up. The clumps (C-MSCs) were treated with LPS and assessed for Adenosine triphosphate (ATP) and OP. Raman spectroscopy was used to analyze calcium salts, DNA, and proline/hydroxyproline. Multiplexed ELISA was performed to assess LPS induced local inflammation. Results: The proliferation of PDLSCs decreased with LPS. On Day 28, LPS-treated cells showed a reduction in their OP. C-MSCs with LPS did not show a decrease in ATP production. Principal bands identified in Raman analysis were the P–O bond at 960 cm−1 of the mineral component, 785 cm−1, and 855 cm−1 showing qualitative changes in OP, proliferation, and proline/hydroxyproline content, respectively. ELISA confirmed increased levels of IL-6 and IL-8 but with the absence of TNF-α and IL-1β secretion. Conclusions: These observations demonstrate that C-MSCs are more resistant to the effects of LPS than cells in monolayer cell culture. Though LPS stimulation of C-MSCs creates an early pro-inflammatory milieu by secreting IL-6 and IL-8, PDLSCs possess inactivated TNF promoter and an ineffective caspase-1 activating process.

scholarly journals EZH2 reduction is an essential mechanoresponse for the maintenance of super-enhancer polarization against compressive stress in human periodontal ligament stem cells

2020 ◽  
Vol 11 (9) ◽  
Author(s):  
Qian Li ◽  
Xiwen Sun ◽  
Yunyi Tang ◽  
Yanan Qu ◽  
Yanheng Zhou ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mechanical Stress ◽  
Periodontal Ligament ◽  
Compressive Force ◽  
Mechanical Stimuli ◽  
Periodontal Ligament Stem Cells ◽  
Super Enhancer ◽  
Ezh2 Expression ◽  
A Genome ◽  
Temporal Dimensions

Abstract Despite the ubiquitous mechanical cues at both spatial and temporal dimensions, cell identities and functions are largely immune to the everchanging mechanical stimuli. To understand the molecular basis of this epigenetic stability, we interrogated compressive force-elicited transcriptomic changes in mesenchymal stem cells purified from human periodontal ligament (PDLSCs), and identified H3K27me3 and E2F signatures populated within upregulated and weakly downregulated genes, respectively. Consistently, expressions of several E2F family transcription factors and EZH2, as core methyltransferase for H3K27me3, decreased in response to mechanical stress, which were attributed to force-induced redistribution of RB from nucleoplasm to lamina. Importantly, although epigenomic analysis on H3K27me3 landscape only demonstrated correlating changes at one group of mechanoresponsive genes, we observed a genome-wide destabilization of super-enhancers along with aberrant EZH2 retention. These super-enhancers were tightly bounded by H3K27me3 domain on one side and exhibited attenuating H3K27ac deposition and flattening H3K27ac peaks along with compensated EZH2 expression after force exposure, analogous to increased H3K27ac entropy or decreased H3K27ac polarization. Interference of force-induced EZH2 reduction could drive actin filaments dependent spatial overlap between EZH2 and super-enhancers and functionally compromise the multipotency of PDLSC following mechanical stress. These findings together unveil a specific contribution of EZH2 reduction for the maintenance of super-enhancer stability and cell identity in mechanoresponse.

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