Resveratrol Attenuates High Glucose-Induced Osteoblast Dysfunction via AKT/GSK3β/FYN-Mediated NRF2 Activation

Osteoblast dysfunction, induced by high glucose (HG), negatively impacts bone homeostasis and contributes to the pathology of diabetic osteoporosis (DOP). One of the most widely recognized mechanisms for osteoblast dysfunction is oxidative stress. Resveratrol (RES) is a bioactive antioxidant compoun...

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Main Authors: Yue Xuan, Jie Wang, Xiaohui Zhang, Jiahao Li, Qingbo Liu, Guangping Lu, Mengjie Xiao, Ting Gao, Yuanfang Guo, Cong Cao, Ou Chen, Kunli Wang, Yufeng Tang, Junlian Gu
Format: Article
Language:English
Published: Frontiers Media S.A. 2022-05-01
Series:Frontiers in Pharmacology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fphar.2022.862618/full
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author Yue Xuan
Jie Wang
Xiaohui Zhang
Jie Wang
Jiahao Li
Qingbo Liu
Guangping Lu
Mengjie Xiao
Ting Gao
Yuanfang Guo
Cong Cao
Ou Chen
Kunli Wang
Yufeng Tang
Junlian Gu
author_facet Yue Xuan
Jie Wang
Xiaohui Zhang
Jie Wang
Jiahao Li
Qingbo Liu
Guangping Lu
Mengjie Xiao
Ting Gao
Yuanfang Guo
Cong Cao
Ou Chen
Kunli Wang
Yufeng Tang
Junlian Gu
author_sort Yue Xuan
collection DOAJ
description Osteoblast dysfunction, induced by high glucose (HG), negatively impacts bone homeostasis and contributes to the pathology of diabetic osteoporosis (DOP). One of the most widely recognized mechanisms for osteoblast dysfunction is oxidative stress. Resveratrol (RES) is a bioactive antioxidant compound to combat oxidative damage. However, its role in the protection of HG-induced osteoblast dysfunction has not been clarified. Therefore, our study aimed to explore potential regulatory mechanisms of RES for attenuating HG-induced osteoblast dysfunction. Our results showed that osteoblast dysfunction under HG condition was significantly ameliorated by RES via the activation of nuclear factor erythroid 2-related factor (NRF2) to suppress oxidative stress. Furthermore, using Nrf2-shRNA and wortmannin, we identified that activation of NRF2 via RES was regulated by the AKT/glycogen synthase kinase 3β (GSK3β)/FYN axis.
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spelling doaj.art-ff32628c761e4419b86f6e37730a4af52022-12-22T03:27:56ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122022-05-011310.3389/fphar.2022.862618862618Resveratrol Attenuates High Glucose-Induced Osteoblast Dysfunction via AKT/GSK3β/FYN-Mediated NRF2 ActivationYue Xuan0Jie Wang1Xiaohui Zhang2Jie Wang3Jiahao Li4Qingbo Liu5Guangping Lu6Mengjie Xiao7Ting Gao8Yuanfang Guo9Cong Cao10Ou Chen11Kunli Wang12Yufeng Tang13Junlian Gu14School of Nursing and Rehabilitation, Cheeloo College of Medicine, Shandong University, Jinan, ChinaSchool of Nursing and Rehabilitation, Cheeloo College of Medicine, Shandong University, Jinan, ChinaSchool of Nursing and Rehabilitation, Cheeloo College of Medicine, Shandong University, Jinan, ChinaSchool of Nursing and Rehabilitation, Cheeloo College of Medicine, Shandong University, Jinan, ChinaSchool of Nursing and Rehabilitation, Cheeloo College of Medicine, Shandong University, Jinan, ChinaSchool of Nursing and Rehabilitation, Cheeloo College of Medicine, Shandong University, Jinan, ChinaSchool of Nursing and Rehabilitation, Cheeloo College of Medicine, Shandong University, Jinan, ChinaSchool of Nursing and Rehabilitation, Cheeloo College of Medicine, Shandong University, Jinan, ChinaSchool of Nursing and Rehabilitation, Cheeloo College of Medicine, Shandong University, Jinan, ChinaSchool of Nursing and Rehabilitation, Cheeloo College of Medicine, Shandong University, Jinan, ChinaSchool of Nursing and Rehabilitation, Cheeloo College of Medicine, Shandong University, Jinan, ChinaSchool of Nursing and Rehabilitation, Cheeloo College of Medicine, Shandong University, Jinan, ChinaSchool of Nursing and Rehabilitation, Cheeloo College of Medicine, Shandong University, Jinan, ChinaDepartment of Orthopedic Surgery, The First Affiliated Hospital of Shandong First Medical University, Jinan, ChinaSchool of Nursing and Rehabilitation, Cheeloo College of Medicine, Shandong University, Jinan, ChinaOsteoblast dysfunction, induced by high glucose (HG), negatively impacts bone homeostasis and contributes to the pathology of diabetic osteoporosis (DOP). One of the most widely recognized mechanisms for osteoblast dysfunction is oxidative stress. Resveratrol (RES) is a bioactive antioxidant compound to combat oxidative damage. However, its role in the protection of HG-induced osteoblast dysfunction has not been clarified. Therefore, our study aimed to explore potential regulatory mechanisms of RES for attenuating HG-induced osteoblast dysfunction. Our results showed that osteoblast dysfunction under HG condition was significantly ameliorated by RES via the activation of nuclear factor erythroid 2-related factor (NRF2) to suppress oxidative stress. Furthermore, using Nrf2-shRNA and wortmannin, we identified that activation of NRF2 via RES was regulated by the AKT/glycogen synthase kinase 3β (GSK3β)/FYN axis.https://www.frontiersin.org/articles/10.3389/fphar.2022.862618/fullresveratroldiabetesosteoblast dysfunctionoxidative stressNRF2
spellingShingle Yue Xuan
Jie Wang
Xiaohui Zhang
Jie Wang
Jiahao Li
Qingbo Liu
Guangping Lu
Mengjie Xiao
Ting Gao
Yuanfang Guo
Cong Cao
Ou Chen
Kunli Wang
Yufeng Tang
Junlian Gu
Resveratrol Attenuates High Glucose-Induced Osteoblast Dysfunction via AKT/GSK3β/FYN-Mediated NRF2 Activation
Frontiers in Pharmacology
resveratrol
diabetes
osteoblast dysfunction
oxidative stress
NRF2
title Resveratrol Attenuates High Glucose-Induced Osteoblast Dysfunction via AKT/GSK3β/FYN-Mediated NRF2 Activation
title_full Resveratrol Attenuates High Glucose-Induced Osteoblast Dysfunction via AKT/GSK3β/FYN-Mediated NRF2 Activation
title_fullStr Resveratrol Attenuates High Glucose-Induced Osteoblast Dysfunction via AKT/GSK3β/FYN-Mediated NRF2 Activation
title_full_unstemmed Resveratrol Attenuates High Glucose-Induced Osteoblast Dysfunction via AKT/GSK3β/FYN-Mediated NRF2 Activation
title_short Resveratrol Attenuates High Glucose-Induced Osteoblast Dysfunction via AKT/GSK3β/FYN-Mediated NRF2 Activation
title_sort resveratrol attenuates high glucose induced osteoblast dysfunction via akt gsk3β fyn mediated nrf2 activation
topic resveratrol
diabetes
osteoblast dysfunction
oxidative stress
NRF2
url https://www.frontiersin.org/articles/10.3389/fphar.2022.862618/full
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