Metformin suppresses Oxidative Stress induced by High Glucose via Activation of the Nrf2/HO-1 Signaling Pathway in Type 2 Diabetic Osteoporosis

作者：Chen, Bohao; He, Qi; Yang, Junzheng; Pan, Zhaofeng; Xiao, Jiacong; Chen, Weijian; Chi, Weijin; Li, Miao; Li, Shaocong; Zeng, Jiaxu; Chen, Chuyi; Wang, FanChen; Pang, Xinyuan; Yi, Yanzi; Tu, Haitao; Wang, Haibin^*; Chen, Peng^*

来源：Life Sciences, 2023, 312: 121092.

DOI：10.1016/j.lfs.2022.121092

• Metformin
• Type 2 diabetic osteoporosis
• Oxidative stress
• Nrf2
• HO-1 signaling pathway

Background: Metformin (MET) is widely used as a first-line hypoglycemic agent for the treatment of type 2 diabetes mellitus (T2DM) and was also confirmed to have a therapeutic effect on type 2 diabetic osteoporosis (T2DOP). However, the potential mechanisms of MET in the treatment of T2DOP are unclear.Objective: To clarify the effect of MET in T2DOP and to explore the potential mechanism of MET in the treatment of T2DOP.Methods: In vitro, we used MC3T3-E1 cells to study the effects of MET on osteogenic differentiation and anti -oxidative stress injury in a high glucose (Glucose 25 mM) environment. In vivo, we directly used db/db mice as a T2DOP model and assessed the osteoprotective effects of MET by Micro CT and histological analysis.Results: In vitro, we found that MET increased ALP activity in MC3T3-E1 cells in a high-glucose environment, promoted the formation of bone mineralized nodules, and upregulated the expression of the osteogenesis-related transcription factors RUNX2, Osterix, and COL1A1-related genes. In addition, MET was able to reduce high glucose-induced reactive oxygen species (ROS) production. In studies on the underlying mechanisms, we found that MET activated the Nrf2/HO-1 signaling pathway and alleviated high-glucose-induced oxidative stress injury. In vivo results showed that MET reduced bone loss and bone microarchitecture destruction in db/db mice. Conclusion: Our results suggest that MET can activate the Nrf2/HO-1 signaling pathway to regulate the inhibition of osteogenic differentiation induced by high glucose thereby protecting T2DOP.

• 单位
  广州中医药大学; 1; 吉林大学