AUTHOR=Xuan Yue , Wang Jie , Zhang Xiaohui , Wang Jie , Li Jiahao , Liu Qingbo , Lu Guangping , Xiao Mengjie , Gao Ting , Guo Yuanfang , Cao Cong , Chen Ou , Wang Kunli , Tang Yufeng , Gu Junlian 

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

JOURNAL=Frontiers in Pharmacology

VOLUME=Volume 13 - 2022

YEAR=2022

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2022.862618

DOI=10.3389/fphar.2022.862618

ISSN=1663-9812

ABSTRACT=Osteoblast dysfunction, induced by high glucose (HG), exerts a negative impact on 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. Here, our results showed that osteoblast dysfunction under HG condition was significantly ameliorated by RES via 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 AKT/glycogen synthase kinase 3β (GSK3β)/FYN axis.