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Resveratrol Attenuates High Glucose-Induced Osteoblast Dysfunction via AKT/GSK3β/FYN-Mediated NRF2 Activation
Yue Xuan1, Jie Wang1, Xiaohui Zhang1
1School of Nursing and Rehabilitation, Cheeloo College of Medicine, Shandong University, Jinan, China.
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 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.
Insights
Resveratrol protects against high glucose-induced osteoblast dysfunction by activating NRF2 to reduce oxidative stress. This protective effect is mediated by the AKT/GSK3β/FYN signaling pathway.
Area of Science:
- Biochemistry
- Cell Biology
- Molecular Biology
Background:
- High glucose (HG) induces osteoblast dysfunction, contributing to diabetic osteoporosis (DOP).
- Oxidative stress is a key mechanism underlying HG-induced osteoblast dysfunction.
- Resveratrol (RES) is an antioxidant with potential therapeutic benefits.
Purpose of the Study:
- To investigate the protective mechanisms of Resveratrol (RES) against high glucose (HG)-induced osteoblast dysfunction.
- To explore the role of nuclear factor erythroid 2-related factor (NRF2) in RES-mediated protection.
- To elucidate the signaling pathway regulating NRF2 activation by RES.
Main Methods:
- Cell culture models of high glucose-induced osteoblast dysfunction.
- Resveratrol treatment and NRF2 activation assays.
- NRF2-shRNA knockdown and wortmannin treatment to investigate the AKT/GSK3β/FYN axis.
Main Results:
- Resveratrol significantly ameliorated osteoblast dysfunction under high glucose conditions.
- RES-induced protection was associated with the activation of NRF2, suppressing oxidative stress.
- The AKT/glycogen synthase kinase 3β (GSK3β)/FYN pathway was identified as a regulator of RES-mediated NRF2 activation.
Conclusions:
- Resveratrol protects osteoblasts from high glucose-induced dysfunction by activating NRF2 and reducing oxidative stress.
- The AKT/GSK3β/FYN signaling pathway plays a crucial role in mediating Resveratrol's effects on NRF2.
- These findings highlight Resveratrol as a potential therapeutic agent for diabetic osteoporosis.
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