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.

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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