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白藜芦醇减轻高糖诱导的成骨细胞功能障碍:AKT/GSK3β/FYN介导的NRF2激活

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

作者信息

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

机构信息

School of Nursing and Rehabilitation, Cheeloo College of Medicine, Shandong University, Jinan, China.

Department of Orthopedic Surgery, The First Affiliated Hospital of Shandong First Medical University, Jinan, China.

出版信息

Front Pharmacol. 2022 May 23;13:862618. doi: 10.3389/fphar.2022.862618. eCollection 2022.

Abstract

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

摘要

高糖(HG)诱导的成骨细胞功能障碍对骨稳态产生负面影响,并导致糖尿病性骨质疏松症(DOP)的病理过程。成骨细胞功能障碍最广为人知的机制之一是氧化应激。白藜芦醇(RES)是一种具有生物活性的抗氧化化合物,可对抗氧化损伤。然而,其在保护HG诱导的成骨细胞功能障碍中的作用尚未阐明。因此,我们的研究旨在探索RES减轻HG诱导的成骨细胞功能障碍的潜在调控机制。我们的结果表明,RES通过激活核因子红细胞2相关因子(NRF2)以抑制氧化应激,显著改善了HG条件下的成骨细胞功能障碍。此外,使用短发夹RNA(shRNA)和渥曼青霉素,我们确定NRF2的激活 RES受AKT/糖原合酶激酶3β(GSK3β)/FYN轴调控。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5274/9169221/aac9a6acb69a/fphar-13-862618-g001.jpg

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