DNA Demethylation Rescues the Impaired Osteogenic Differentiation Ability of Human Periodontal Ligament Stem Cells in High Glucose

Li, Zhi; Chen, Tian; Sun, Wei; Yuan, Zongyi; Yu, Man; Chen, Guoqing; Guo, Weihua; Xiao, Jingang; Tian, Weidong

doi:10.1038/srep27447

Cited by 37 publications

(44 citation statements)

References 53 publications

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“…For a further analytical approach, the mRNA expression levels of ALP, OSX, RUNX2 and COL1 were measured by RT-qPCR. During osteogenesis, numerous osteogenic marker genes of hPDLSCs, including ALP, COL1, OSX, and RUNX2, can be increased (31). ALP, as an early-stage osteogenic-specific gene, serves an important role in bone formation and mineralization (15).…”

Section: Discussionmentioning

confidence: 99%

Gold nanoparticles promote osteogenic differentiation of human periodontal ligament stem cells via the p38 MAPK signaling pathway

Niu

Yuan

et al. 2017

Molecular Medicine Reports

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Gold nanoparticles (AuNPs) are a promising material for use in regenerative medicine due to their biocompatibility and easy functionalization with biomolecules including growth factors, DNA and peptides. In the present study, transmission electron microscopy indicated that the AuNPs were monodisperse and spherical in shape, with an estimated average diameter of 13 nm. And the cellular effects of AuNPs on the osteogenic differentiation of human periodontal ligament stem cells (hPDLSCs) and the associated signaling pathways in cell differentiation were investigated based on histochemical analysis of alkaline phosphatase activity and mineralization, quantitative polymerase chain reaction, and western blotting. The results indicated that AuNPs enhanced the differentiation of hPDLSCs into osteoblasts, increasing their osteogenic transcriptional profile including alkaline phosphatase, osterix, collagen type I and runt‑related transcription factor 2 (RUNX2) and activating the p38 mitogen‑activated protein kinase (MAPK) signaling pathway. Furthermore, AuNPs increased the protein level of RUNX2, which is crucial for osteogenic differentiation. These results suggested that AuNPs stimulate the osteogenesis of hPDLSCs partially via activation of the p38 MAPK signaling pathway.

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Section: Discussionmentioning

confidence: 99%

Gold nanoparticles promote osteogenic differentiation of human periodontal ligament stem cells via the p38 MAPK signaling pathway

Niu

Yuan

et al. 2017

Molecular Medicine Reports

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“…In line with this suggestion, in‐vitro application of 5‐aza‐2′‐deoxycytidine to decrease DNA‐methylation levels in human periodontal ligament stem cells was capable of rescuing the osteogenic capacity of these cells under high‐glucose conditions . A subsequent animal experiment showed that diabetic rats with increased DNA‐methylation levels in their periodontal ligaments exhibited reduced bone mass and bone density . It seems that suppression of DNA methylation could enhance the osteogenic capacity of human periodontal ligament stem cells even in pathological states, such as diabetes mellitus.…”

Section: Methodsmentioning

confidence: 70%

Role of epigenetics in alveolar bone resorption and regeneration around periodontal and peri‐implant tissues

Asa’ad

Monje

Larsson

2019

European J Oral Sciences

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Periodontitis and peri‐implantitis are multifactorial diseases characterized by alveolar bone destruction mediated by the host response to a microbial challenge. Alveolar bone resorption mediated by epigenetics could be one of the mechanisms responsible for this destruction of alveolar bone. The relationship between epigenetic modifications and bone metabolism has been thoroughly investigated in bone remodeling, cancer, and rheumatoid arthritis, but evidence is low regarding the relationship between epigenetic modifications and alveolar bone loss related to periodontal and peri‐implant diseases. Therefore, we conducted a review of the pertinent literature based on a priori‐formulated focused questions and a screening strategy, in an attempt to comprehend the role of different epigenetic mechanisms in alveolar bone loss and to determine the current state with respect to their possible therapeutic applications in regenerative medicine. The review showed that the roles of DNA methylation, histone modifications, and non‐coding RNAs in bone loss have been investigated. The results indicate that epigenetic mechanisms can participate in periodontal and peri‐implant alveolar bone breakdown, suggesting their potential as therapeutic targets in alveolar bone regeneration. However, there is still only preliminary information regarding the possible therapeutic utility of these epigenetic mechanisms, suggesting a need for basic and translational research to assess the potential of such mechanisms in promoting alveolar bone regeneration.

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“…DNA methylation is a critical regulator of stem cell differentiation. Interestingly, it has been described that the DNA methyltransferase inhibitor 5-aza-2 -deoxycytidine (5-aza-dC) is able to increase the stemness of periodontal ligament stem cells (PDLSCs), and also to enhance the reprogramming efficiency of human gingival mesenchymal stem cells (hGMSCs) [26,78]. Another report showed that a short pre-application of 5-aza-dC for 24 h increased the responsiveness of DPSCs to osteogenic differentiation protocols [79], a similar result to the one obtained after preconditioning DPSCs for 48 h with BIO or WNT-3A, as we showed in our own previous research [13].…”

Section: Discussionmentioning

confidence: 99%

Wnt-3a Induces Epigenetic Remodeling in Human Dental Pulp Stem Cells

Uribe-Etxebarria

García-Gallastegui

Pérez-Garrastachu

et al. 2020

Cells

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Dental pulp stem cells (DPSCs) from adult teeth show the expression of a very complete repertoire of stem pluripotency core factors and a high plasticity for cell reprogramming. Canonical Wnt and Notch signaling pathways regulate stemness and the expression of pluripotency core factors in DPSCs, and even very short-term (48 h) activations of the Wnt pathway induce a profound remodeling of DPSCs at the physiologic and metabolic levels. In this work, DPSC cultures were exposed to treatments modulating Notch and Wnt signaling, and also induced to differentiate to osteo/adipocytes. DNA methylation, histone acetylation, histone methylation, and core factor expression levels where assessed by mass spectroscopy, Western blot, and qPCR. A short-term activation of Wnt signaling by WNT-3A induced a genomic DNA demethylation, and increased histone acetylation and histone methylation in DPSCs. The efficiency of cell reprogramming methods relies on the ability to surpass the epigenetic barrier, which determines cell lineage specificity. This study brings important information about the regulation of the epigenetic barrier by Wnt signaling in DPSCs, which could contribute to the development of safer and less aggressive reprogramming methodologies with a view to cell therapy.

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DNA Demethylation Rescues the Impaired Osteogenic Differentiation Ability of Human Periodontal Ligament Stem Cells in High Glucose

Cited by 37 publications

References 53 publications

Gold nanoparticles promote osteogenic differentiation of human periodontal ligament stem cells via the p38 MAPK signaling pathway

Gold nanoparticles promote osteogenic differentiation of human periodontal ligament stem cells via the p38 MAPK signaling pathway

Role of epigenetics in alveolar bone resorption and regeneration around periodontal and peri‐implant tissues

Wnt-3a Induces Epigenetic Remodeling in Human Dental Pulp Stem Cells

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