Erythropoietin Activates Autophagy to Regulate Apoptosis and Angiogenesis of Periodontal Ligament Stem Cells via the Akt/ERK1/2/BAD Signaling Pathway under Inflammatory Microenvironment

Background. Angiogenic tissue engineering is a vital problem waiting to be settled for periodontal regeneration. Erythropoietin, a multieffect cytokine, has been reported as a protective factor for cell fate. According to our previous study, erythropoietin has a significantly angiogenic effect on pe...

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Main Authors: Denghao Huang, Jie Lei, Xingrui Li, Zhonghao Jiang, Maoxuan Luo, Yao Xiao
Format: Article
Language:English
Published: Wiley 2022-01-01
Series:Stem Cells International
Online Access:http://dx.doi.org/10.1155/2022/9806887
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author Denghao Huang
Jie Lei
Xingrui Li
Zhonghao Jiang
Maoxuan Luo
Yao Xiao
author_facet Denghao Huang
Jie Lei
Xingrui Li
Zhonghao Jiang
Maoxuan Luo
Yao Xiao
author_sort Denghao Huang
collection DOAJ
description Background. Angiogenic tissue engineering is a vital problem waiting to be settled for periodontal regeneration. Erythropoietin, a multieffect cytokine, has been reported as a protective factor for cell fate. According to our previous study, erythropoietin has a significantly angiogenic effect on periodontal ligament stem cells. To further explore its potential effects and mechanism, we studied biological behaviors of periodontal ligament stem cells under inflammatory microenvironment induced by different concentrations (0, 10, 20, 50, and 100 ng/mL) of tumor necrosis factor-α (TNF-α) and examined how different concentrations (0, 5, 10, 20, and 50 IU/mL) of erythropoietin changed biological behaviors of periodontal ligament stem cells. Materials and Methods. Cell Counting Kit-8 was used for cell proliferation assay. Annexin V-PI-FITC was used for cell apoptosis through flow cytometry. Matrigel plug was adopted to measure the angiogenic capacity in vitro. RNA sequencing was used to detect the downstream signaling pathway. Quantitative real-time polymerase chain reaction was conducted to examine mRNA expression level. Western blot and immunofluorescence were applied to testify the protein expression level. Results. Periodontal ligament stem cells upregulated apoptosis and suppressed autophagy and angiogenesis under inflammatory microenvironment. Erythropoietin could activate autophagy to rescue apoptosis and angiogenesis levels of periodontal ligament stem cells through the Akt/Erk1/2/BAD signaling pathway under inflammatory microenvironment. Conclusions. Erythropoietin could protect periodontal ligament stem cells from inflammatory microenvironment, which provided a novel theory for periodontal regeneration.
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spelling doaj-art-ddc22df8b3dc48ecb0086be33464ca742025-02-03T06:08:45ZengWileyStem Cells International1687-96782022-01-01202210.1155/2022/9806887Erythropoietin Activates Autophagy to Regulate Apoptosis and Angiogenesis of Periodontal Ligament Stem Cells via the Akt/ERK1/2/BAD Signaling Pathway under Inflammatory MicroenvironmentDenghao Huang0Jie Lei1Xingrui Li2Zhonghao Jiang3Maoxuan Luo4Yao Xiao5Luzhou Key Laboratory of Orofacial Reconstruction and RegenerationLuzhou Key Laboratory of Orofacial Reconstruction and RegenerationLuzhou Key Laboratory of Orofacial Reconstruction and RegenerationLuzhou Key Laboratory of Orofacial Reconstruction and RegenerationLuzhou Key Laboratory of Orofacial Reconstruction and RegenerationLuzhou Key Laboratory of Orofacial Reconstruction and RegenerationBackground. Angiogenic tissue engineering is a vital problem waiting to be settled for periodontal regeneration. Erythropoietin, a multieffect cytokine, has been reported as a protective factor for cell fate. According to our previous study, erythropoietin has a significantly angiogenic effect on periodontal ligament stem cells. To further explore its potential effects and mechanism, we studied biological behaviors of periodontal ligament stem cells under inflammatory microenvironment induced by different concentrations (0, 10, 20, 50, and 100 ng/mL) of tumor necrosis factor-α (TNF-α) and examined how different concentrations (0, 5, 10, 20, and 50 IU/mL) of erythropoietin changed biological behaviors of periodontal ligament stem cells. Materials and Methods. Cell Counting Kit-8 was used for cell proliferation assay. Annexin V-PI-FITC was used for cell apoptosis through flow cytometry. Matrigel plug was adopted to measure the angiogenic capacity in vitro. RNA sequencing was used to detect the downstream signaling pathway. Quantitative real-time polymerase chain reaction was conducted to examine mRNA expression level. Western blot and immunofluorescence were applied to testify the protein expression level. Results. Periodontal ligament stem cells upregulated apoptosis and suppressed autophagy and angiogenesis under inflammatory microenvironment. Erythropoietin could activate autophagy to rescue apoptosis and angiogenesis levels of periodontal ligament stem cells through the Akt/Erk1/2/BAD signaling pathway under inflammatory microenvironment. Conclusions. Erythropoietin could protect periodontal ligament stem cells from inflammatory microenvironment, which provided a novel theory for periodontal regeneration.http://dx.doi.org/10.1155/2022/9806887
spellingShingle Denghao Huang
Jie Lei
Xingrui Li
Zhonghao Jiang
Maoxuan Luo
Yao Xiao
Erythropoietin Activates Autophagy to Regulate Apoptosis and Angiogenesis of Periodontal Ligament Stem Cells via the Akt/ERK1/2/BAD Signaling Pathway under Inflammatory Microenvironment
Stem Cells International
title Erythropoietin Activates Autophagy to Regulate Apoptosis and Angiogenesis of Periodontal Ligament Stem Cells via the Akt/ERK1/2/BAD Signaling Pathway under Inflammatory Microenvironment
title_full Erythropoietin Activates Autophagy to Regulate Apoptosis and Angiogenesis of Periodontal Ligament Stem Cells via the Akt/ERK1/2/BAD Signaling Pathway under Inflammatory Microenvironment
title_fullStr Erythropoietin Activates Autophagy to Regulate Apoptosis and Angiogenesis of Periodontal Ligament Stem Cells via the Akt/ERK1/2/BAD Signaling Pathway under Inflammatory Microenvironment
title_full_unstemmed Erythropoietin Activates Autophagy to Regulate Apoptosis and Angiogenesis of Periodontal Ligament Stem Cells via the Akt/ERK1/2/BAD Signaling Pathway under Inflammatory Microenvironment
title_short Erythropoietin Activates Autophagy to Regulate Apoptosis and Angiogenesis of Periodontal Ligament Stem Cells via the Akt/ERK1/2/BAD Signaling Pathway under Inflammatory Microenvironment
title_sort erythropoietin activates autophagy to regulate apoptosis and angiogenesis of periodontal ligament stem cells via the akt erk1 2 bad signaling pathway under inflammatory microenvironment
url http://dx.doi.org/10.1155/2022/9806887
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