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=13

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=<p>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 <italic>via</italic> the activation of nuclear factor erythroid 2-related factor (NRF2) to suppress oxidative stress. Furthermore, using <italic>Nrf2</italic>-shRNA and wortmannin, we identified that activation of NRF2 <italic>via</italic> RES was regulated by the AKT/glycogen synthase kinase 3β (GSK3β)/FYN axis.</p>