Role of YAP1 gene in proliferation, osteogenic differentiation, and apoptosis of human periodontal ligament stem cells induced by TNF‐α

Periodontitis is a chronic disease that includes the pathologic loss of periodontal tissue and alveolar bone. The inflammatory environment in periodontitis impairs the osteogenic differentiation potential and depresses the regeneration capacity of human periodontal ligament stem cells (hPDLSCs). Since Forkhead box protein O1 (FoxO1) plays an important role in redox balance and bone formation, we investigated the role of FoxO1 in oxidative stress resistance and osteogenic differentiation in an inflammatory environment by overexpressing FoxO1 in hPDLSCs. First, we found that FoxO1 overexpression reduced reactive oxygen species (ROS) accumulation, decreased malondialdehyde (MDA) levels, and elevated antioxidant potential under oxidative condition. Next, the overexpression of FoxO1 protected hPDLSCs against oxidative damage, which involved stabilization of the mitochondrial membrane potential. Third, overexpressed FoxO1 promoted extracellular matrix (ECM) mineralization and increased the expression of the osteogenic markers Runx2 and SP7 in the inflammatory environment. These results indicated that FoxO1 overexpression in hPDLSCs has an anti-inflammatory effect, increases antioxidative capacity, and positively regulates osteogenesis in a mimicked inflammatory environment.

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

Journal of Personalized Medicine ◽

10.3390/jpm11060528 ◽

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.

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Stromal cell‐derived factor‐1/Exendin‐4 cotherapy facilitates the proliferation, migration and osteogenic differentiation of human periodontal ligament stem cells in vitro and promotes periodontal bone regeneration in vivo

Cell Proliferation ◽

10.1111/cpr.12997 ◽

2021 ◽

Author(s):

Qianyu Liang ◽

Lingqian Du ◽

Rui Zhang ◽

Wenyan Kang ◽

Shaohua Ge

Keyword(s):

Stem Cells ◽

Bone Regeneration ◽

Osteogenic Differentiation ◽

Periodontal Ligament ◽

Stromal Cell ◽

Periodontal Ligament Stem Cells ◽

Stromal Cell Derived Factor

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

European Journal of Histochemistry ◽

10.4081/ejh.2017.2826 ◽

2017 ◽

Vol 61 (3) ◽

Cited By ~ 8

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

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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