Osteoinductive function of fucoidan on periodontal ligament stem cells: Role of PI3K/Akt and Wnt/β‐catenin signaling pathways

Oral Diseases ◽  
2021 ◽  
Author(s):  
Na Young Shim ◽  
Jae‐In Ryu ◽  
Jung Sun Heo
Keyword(s):  
Stem Cells ◽  
Signaling Pathways ◽  
Periodontal Ligament ◽  
Periodontal Ligament Stem Cells

scholarly journals Porphyromonas gingivalis lipopolysaccharide stimulation in human periodontal ligament stem cells: role of epigenetic modifications to the inflammation

2017 ◽  
Vol 61 (3) ◽  
Author(s):  
Francesca Diomede ◽  
Soundara Rajan Thangavelu ◽  
Ilaria Merciaro ◽  
Monica D'Orazio ◽  
Placido Bramanti ◽  
...  
Keyword(s):  
Stem Cells ◽  
Porphyromonas Gingivalis ◽  
Inflammatory Disease ◽  
Periodontal Ligament ◽  
Model System ◽  
Epigenetic Mechanism ◽  
Periodontal Ligament Stem Cells ◽  
Porphyromonas Gingivalis Lipopolysaccharide

<p>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 <em>in vitro</em> model system. hPDLSCs were treated with lipopolysaccharide of <em>Porphyromonas gingivalis</em> 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 <em>P. gingivalis </em>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 <em>P. gingivalis </em>lipopolysaccharide markedly regulate the genes involved in epigenetic mechanism, which may result in inflammation induction. We propose that <em>P. gingivalis </em>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.</p>

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

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.

scholarly journals Transcriptome analysis reveals the mechanism of stromal cell-derived factor-1 and exendin-4 synergistically promoted periodontal ligament stem cells osteogenic differentiation

PeerJ ◽  
2021 ◽  
Vol 9 ◽  
pp. e12091
Author(s):  
Wenyan Kang ◽  
Lingqian Du ◽  
Qianyu Liang ◽  
Rui Zhang ◽  
Chunxu Lv ◽  
...  
Keyword(s):  
Stem Cells ◽  
Osteogenic Differentiation ◽  
Signaling Pathways ◽  
Periodontal Ligament ◽  
Stromal Cell ◽  
Expression Patterns ◽  
Gene Clusters ◽  
Gene Set Enrichment Analysis ◽  
Periodontal Ligament Stem Cells ◽  
Stromal Cell Derived Factor

Stromal cell-derived factor-1 (SDF-1) and Exendin-4 (EX-4) play beneficial roles in promoting periodontal ligament stem cells (PDLSCs) osteogenic differentiation, while the detailed mechanism has not been clarified. In this study, we aimed to evaluate the biological mechanism of SDF-1 and EX-4 alone or synergistic application in regulating PDLSCs differentiation by RNA-sequencing (RNA-seq). A total of 110, 116 and 109 differentially expressed genes (DEGs) were generated in osteogenic medium induced PDLSCs treated by SDF-1, EX-4, and SDF-1+EX-4, respectively. The DEGs in SDF-1 group were enriched in signal transduction related signaling pathways; the DEGs in EX-4 group were enriched in metabolism and biosynthesis-related pathways; and the DEGs generated in SDF-1+EX-4 group were mainly enriched in RNA polymerase II transcription, cell differentiation, chromatin organization, protein phosphorylation pathways. Based on Venn analysis, a total of 37 specific DEGs were identified in SDF-1+EX-4 group, which were mainly enriched in negative regulation of autophagy and cellular component disassembly signaling pathways. Short time-series expression miner (STEM) analysis grouped all expressed genes of PDLSCs into 49 clusters according to the dynamic expression patterns and 25 genes, including NRSN2, CHD9, TUBA1A, distributed in 10 gene clusters in SDF-1+EX-4 treated PDLSCs were significantly up-regulated compared with the SDF-1 and EX-4 alone groups. The gene set enrichment analysis indicated that SDF-1 could amplify the role of EX-4 in regulating varied signaling pathways, such as type II diabetes mellitus and insulin signaling pathways; while EX-4 could aggravate the effect of SDF-1 on PDLSCs biological roles via regulating primary immunodeficiency, tight junction signaling pathways. In summary, our study confirmed that SDF-1 and EX-4 combined application could enhance PDLSCs biological activity and promote PDLSCs osteogenic differentiation by regulating the metabolism, biosynthesis and immune-related signaling pathways.

scholarly journals Melatonin induces the rejuvenation of long-term ex vivo expanded periodontal ligament stem cells by modulating the autophagic process

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Yi-Zhou Tan ◽  
Xin-Yue Xu ◽  
Ji-Min Dai ◽  
Yuan Yin ◽  
Xiao-Tao He ◽  
...  
Keyword(s):  
Stem Cells ◽  
Signaling Pathways ◽  
Signaling Pathway ◽  
Cellular Senescence ◽  
Periodontal Ligament ◽  
Ex Vivo ◽  
Mtor Signaling ◽  
Mtor Signaling Pathway ◽  
Periodontal Ligament Stem Cells

Abstract Background Stem cells that have undergone long-term ex vivo expansion are most likely functionally compromised (namely cellular senescence) in terms of their stem cell properties and therapeutic potential. Due to its ability to attenuate cellular senescence, melatonin (MLT) has been proposed as an adjuvant in long-term cell expansion protocols, but the mechanism underlying MLT-induced cell rejuvenation remains largely unknown. Methods Human periodontal ligament stem cells (PDLSCs) were isolated and cultured ex vivo for up to 15 passages, and cells from passages 2, 7, and 15 (P2, P7, and P15) were used to investigate cellular senescence and autophagy change in response to long-term expansion and indeed the following MLT treatment. Next, we examined whether MLT could induce cell rejuvenation by restoring the autophagic processes of damaged cells and explored the underlying signaling pathways. In this context, cellular senescence was indicated by senescence-associated β-galactosidase (SA-β-gal) activity and by the expression of senescence-related proteins, including p53, p21, p16, and γ-H2AX. In parallel, cell autophagic processes were evaluated by examining autophagic vesicles (by transmission electronic microscopy), autophagic flux (by assessing mRFP-GFP-LC3-transfected cells), and autophagy-associated proteins (by Western blot assay of Atg7, Beclin-1, LC3-II, and p62). Results We found that long-term in vitro passaging led to cell senescence along with impaired autophagy. As expected, MLT supplementation not only restored cells to a younger state but also restored autophagy in senescent cells. Additionally, we demonstrated that autophagy inhibitors could block MLT-induced cell rejuvenation. When the underlying signaling pathways involved were investigated, we found that the MLT receptor (MT) mediated MLT-related autophagy restoration by regulating the PI3K/AKT/mTOR signaling pathway. Conclusions The present study suggests that MLT may attenuate long-term expansion-caused cellular senescence by restoring autophagy, most likely via the PI3K/AKT/mTOR signaling pathway in an MT-dependent manner. This is the first report identifying the involvement of MT-dependent PI3K/AKT/mTOR signaling in MLT-induced autophagy alteration, indicating a potential of autophagy-restoring agents such as MLT to be used in the development of optimized clinical-scale cell production protocols.

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