The role of lysophosphatidic acid receptor 1 in inflammatory response induced by lipopolysaccharide from Porphyromonas gingivalis in human periodontal ligament stem cells

Periodontitis is a chronic oral inflammatory disease produced by bacteria. Gingival retraction and bone and connective tissues resorption are the hallmarks of this disease. Chronic periodontitis may contribute to the risk of onset or progression of neuroinflammatory pathological conditions, such as Alzheimer’s disease. The main goal of the present study was to investigate if the role of epigenetic modulations is involved in periodontitis using human periodontal ligament stem cells (hPDLSCs) as an in vitro model system. hPDLSCs were treated with lipopolysaccharide of Porphyromonas gingivalis and the expression of proteins associated with DNA methylation and histone acetylation, such as DNMT1 and p300, respectively, and inflammatory transcription factor NF-kB, were examined. Immunofluorescence, Western blot and next generation sequencing results demonstrated that P. gingivalis lipopolysaccharide significantly reduced DNA methylase DNMT1, while it markedly upregulated the level of histone acetyltransferase p300 and NF-kB in hPDLSCs. Our results showed that P. gingivalis lipopolysaccharide markedly regulate the genes involved in epigenetic mechanism, which may result in inflammation induction. We propose that P. gingivalis lipopolysaccharide-treated hPDLSCs could be a potential in vitro model system to study epigenetics modulations associated with periodontitis, which might be helpful to identify novel biomarkers linked to this oral inflammatory disease.

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The Role of Lysophosphatidic Acid Receptor (LPA1) in the Oxygen-Induced Retinal Ganglion Cell Degeneration

Investigative Opthalmology & Visual Science ◽

10.1167/iovs.08-1920 ◽

2009 ◽

Vol 50 (3) ◽

pp. 1290 ◽

Cited By ~ 16

Author(s):

Chun Yang ◽

Josiane Lafleur ◽

Bupe R. Mwaikambo ◽

Tang Zhu ◽

Carmen Gagnon ◽

...

Keyword(s):

Ganglion Cell ◽

Retinal Ganglion Cell ◽

Lysophosphatidic Acid ◽

Retinal Ganglion ◽

Cell Degeneration ◽

Acid Receptor ◽

Lysophosphatidic Acid Receptor

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The Regulatory Role of A Disintegrin and Metalloproteinase 28 on the Biologic Property of Human Periodontal Ligament Stem Cells

Journal of Periodontology ◽

10.1902/jop.2010.090703 ◽

2010 ◽

Vol 81 (6) ◽

pp. 934-944 ◽

Cited By ~ 3

Author(s):

Zheng Zhao ◽

Yi Wang ◽

Dongsheng Wang ◽

Hongchen Liu

Keyword(s):

Stem Cells ◽

Periodontal Ligament ◽

Regulatory Role ◽

Periodontal Ligament Stem Cells ◽

Biologic Property ◽

A Disintegrin And Metalloproteinase

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Pharmacodynamics of siRNARANKL and Oestrogen Loaded MSNs-CADY on Human Periodontal Ligament Stem Cells with Porphyromonas gingivalis infection

10.21203/rs.2.20120/v1 ◽

2020 ◽

Author(s):

Liang Song ◽

Xiaojun Shi ◽

Fengling Hu ◽

Huijuan Chen ◽

Bin Xu ◽

...

Keyword(s):

Stem Cells ◽

Cell Proliferation ◽

Drug Release ◽

Mesoporous Silica ◽

Porphyromonas Gingivalis ◽

Periodontal Ligament ◽

Mesoporous Silica Nanoparticles ◽

Cell Penetrating Peptide ◽

Periodontal Ligament Stem Cells ◽

Cell Penetrating

Abstract Background: Periodontitis irreversibly invades and destroys periodontal supporting tissues, loses the ability of periodontal regeneration and restoration, and eventually leads to tooth loosening and loss. periodontal ligament stem cells (PDLSCs) hold great promises for periodontal tissue regeneration which was the potential target of periodontitis treatment, siRNARANKL and oestrogen can help PDLSCs maintain normal function, however, it was very difficult for siRNARANKL and oestrogen to get into PDLSCs. Here, Cell penetrating peptide CADY was modified on the surface of siRNARANKL and oestrogen loaded mesoporous silica nanoparticles (MSNs) to carry them into Porphyromonas gingivalis infected PDLSCs, Then further affect the proliferation of PDLSCs. Methods: 120-150 nm Mesoporous silica nanoparticles (MSNs) was prepared, and the biocompatibility, loading capacity and drug release properity were tested; MSNs was modified by penetrating peptide CADY and the prepared MSNs/CADY was loaded with siRNARANKL and oestrogen; In vitro drug release of siRNARANKL/MSNs-CADY and oestrogen/MSNs-CADY was tested by using semi-permeable dialysis bag diffusion; Cellular uptake and internalization of FITC-Labeled MSNs and FITC-Labeled MSNs-CADY was observed by use of Laser confocal microscopy; Finally, the effect of siRNARANKL and oestrogen loaded MSNs-CADY on cell proliferation of Porphyromonas gingivalis infected human periodontal ligament stem cells was tested by MTT assay. Results: according to the results, MSNs-CADY with a concentration of 6.25-200 ug/mL have no toxic to PDLSCs; 24.6 mg oestrogen and 0.5 mM siRNARANKL can be loaded into 1mg of MSNs-CADY; and drug loaded MSNs-CADY nanodrug carriers can release siRNARANKL and oestrogen stably for at least 48 h; After modification with cell penetrating peptide CADY, more MSNs-CADY can be taken by PDLSCs. siRNARANKL/oestrogen/MSNs-CADY can increase the proliferation of PDLSCs significantly. Conclusion: siRNARANKL/oestrogen/MSNs-CADY constructed can significantly improve the cell proliferation of P-gingivalis infected PDLSCs, this nano drug carrier has the potential to be used in PDLSCs -based periodontitis treatment, this work provided a useful theoretical basis and therapeutic ideas for the treatment of periodontitis.

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Klotho inhibits H 2 O 2 -induced oxidative stress and apoptosis in periodontal ligament stem cells by regulating UCP2 expression

10.21203/rs.3.rs-24745/v1 ◽

2020 ◽

Author(s):

Lilei Zhu ◽

Hui Xie ◽

Qingqing Liu ◽

Fei Ma ◽

Hao Wu

Keyword(s):

Oxidative Stress ◽

Stem Cells ◽

Chronic Periodontitis ◽

Periodontal Ligament ◽

Gingival Crevicular Fluid ◽

Uncoupling Protein ◽

Transmembrane Protein ◽

Periodontal Ligament Stem Cells ◽

Ucp2 Expression

Abstract Background Periodontitis, known as a human chronic inflammatory disease, has affected the life of millions of individuals. Known risk factors such as metabolic disease and oxidative stress have been reported to be closely associated with the initiation or development of periodontitis. However, the etiology of periodontitis remains unclear. Klotho, a single-pass transmembrane protein, has been widely reported to modulate cellular processes in various diseases. However, the role of Klotho in periodontitis is unknown.Results In this study, we designed and conducted a series of experiments to evaluate the role of Klotho in chronic periodontitis. Our experimental results showed that Klotho was downregulated in the gingival tissues, gingival crevicular fluid (GCF), and periodontal ligament stem cells (PDLSCs) of chronic periodontitis patients. Besides, Klotho upregulated the production of uncoupling protein 2 (UCP2) in H2O2-treated PDLSCs. In function, Klotho inhibited H2O2-induced oxidative stress and cellular apoptosis in PDLSCs. Moreover, the rescue assay suggested that UCP2 knock-down suppressed the effects of Klotho on H2O2-induced oxidative stress and apoptosis in PDLSCs.Conclusions In conclusion, we found that Klotho inhibits H2O2-induced oxidative stress and apoptosis in PDLSCs by regulating UCP2 expression. This novel discovery may provide a potential target for chronic periodontitis treatment.

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Abstract 264: Upstream and Downstream Regulators of Lysophosphatidic Acid Receptor 4 are Critical for Cardiac Differentiation and Repair

Circulation Research ◽

10.1161/res.127.suppl_1.264 ◽

2020 ◽

Vol 127 (Suppl_1) ◽

Author(s):

Hyun-jai Cho ◽

Jin-Woo Lee ◽

Choon-Soo Lee ◽

Hyo-Soo Kim

Keyword(s):

Stem Cells ◽

Transcription Factors ◽

Lysophosphatidic Acid ◽

Functional Significance ◽

Cardiac Differentiation ◽

Specific Marker ◽

Acid Receptor ◽

Lysophosphatidic Acid Receptor ◽

Human Ipscs

The therapeutic application of cell therapy to repair the damaged heart requires a comprehensive understanding of the process of cardiac differentiation of stem cells. We discovered a cardiac-specific marker, lysophosphatidic acid receptor 4 (LPAR4), which is G protein-coupled receptor (GPCR) and demonstrated its functional significance during cardiac differentiation. We screened GPCR expressing on mouse cardiac progenitor cells at differentiation day 3 compared to mouse undifferentiated pluripotent stem cells (PSCs). Among candidates, we identified LPAR4. We have found that in both mouse and human PSCs, LPAR4 has a transient expression pattern during cardiac differentiation. During in vitro differentiation of mouse and human PSCs toward cardiomyocytes, LPAR4 expression peaked for 3-5 days and then and declined immediately. Treatment with ODP (LPAR4 specific agonist) followed by p38MAPK blocker (SB203580) in the cardiac differentiation protocol significantly increased cardiac differentiation efficiency. Then we performed RNA sequencing to find transcription factors that regulate LPAR4. We screened 2-fold up-regulated transcription factors that related to cardiac differentiation during human iPSCs toward cardiomyocytes. The expression of LPAR4 is regulated by SOX17 expression, demonstrating that SOX17 is an upstream regulator of LPAR4. During cardiac differentiation, when knocking down SOX17 by siRNA, the expression of LPAR4 decreased as the expression of SOX17 mRNA decreased, resulting in no progression of cardiac differentiation. Besides, cardiac differentiation did not progress when SOX17 was overexpressed. SOX17 plays a role early in cardiac differentiation and that the expression should be reduced. However, it is assumed that sox17 lentivirus was gene-integrated and continued expression without decreasing expression. SOX17 overexpression needs further study. In conclusion, we demonstrated that LPAR4 is a novel cardiac progenitor cell marker and modulation of the upstream and downstream regulators shown functional significance during cardiac differentiation. Furthermore, our findings provide new insight into cell-free cardiac repair by the modulation of LPAR4 positive cells in the heart. Funding Source: This study was supported by "Strategic Center of Cell and Bio Therapy for Heart, Diabetes & Cancer" (HI17C2085) through the Korea Health Industry Development Institute, funded by the Ministry of Health & Welfare, Republic of Korea.

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