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

被引：39

作者：

Chen, Bohao ^{[1
,2
]}

He, Qi ^{[1
,2
]}

Yang, Junzheng ^{[1
,2
]}

Pan, Zhaofeng ^{[1
,2
]}

Xiao, Jiacong ^{[1
,2
]}

Chen, Weijian ^{[2
,3
]}

Chi, Weijin ^{[1
,2
]}

Li, Miao ^{[1
,2
]}

Li, Shaocong ^{[1
,2
]}

Zeng, Jiaxu ^{[1
,2
]}

Chen, Chuyi ^{[1
,2
]}

Wang, FanChen ^{[1
,2
]}

Pang, Xinyuan ^{[4
]}

Yi, Yanzi ^{[5
]}

Tu, Haitao ^{[6
]}

Wang, Haibin ^{[6
]}

Chen, Peng ^{[6
]}

机构：

[1] Guangzhou Univ Chinese Med, Sch Med 1, 12 Jichang Rd, Baiyun Area, Guangzhou 510405, Peoples R China

[2] Guangzhou Univ Chinese Med, Lingnan Med Res Ctr, Lab Orthopaed & Traumatol, Guangzhou 510405, Peoples R China

[3] Guangzhou Univ Chinese Med, Guangdong Tradit Chinese Med Hosp 2, Guangzhou 510405, Peoples R China

[4] First Hosp Jilin Univ, Dept Neurol, Changchun, Peoples R China

[5] Guangzhou Univ Chinese Med, Affiliated Med Coll 3, Guangzhou 510405, Peoples R China

[6] Guangzhou Univ Chinese Med, Dept Orthopaed, Affiliated Hosp 1, 12 Jichang Rd, Baiyun Area, Guangzhou 510405, Peoples R China

来源：

LIFE SCIENCES | 2023年 / 312卷

基金：

中国国家自然科学基金;

关键词：

Metformin; Type 2 diabetic osteoporosis; Oxidative stress; Nrf2; HO-1 signaling pathway; BONE; MELLITUS; OXIDANTS; LEPTIN; IMPACT; CELLS; MODEL;

D O I：

10.1016/j.lfs.2022.121092

中图分类号：

R-3 [医学研究方法]; R3 [基础医学];

学科分类号：

100103 [病原生物学]; 100218 [急诊医学];

摘要：

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.

引用

页数：12

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