1st School of Medicine, Guangzhou University of Chinese Medicine, 12 Jichang Road, Baiyun Area, Guangzhou 510405, PR China; The Laboratory of Orthopaedics and Traumatology of Lingnan Medical Research Center, Guangzhou University of Chinese Medicine, Guangzhou 510405, PR China.
Guangdong Second Traditional Chinese Medicine Hospital, Guangzhou University of Chinese Medicine, Guangzhou 510405, PR China.
Life Sci. 2023 Jan 1;312:121092. doi: 10.1016/j.lfs.2022.121092. Epub 2022 Oct 21.
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.
To clarify the effect of MET in T2DOP and to explore the potential mechanism of MET in the treatment of T2DOP.
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.
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.
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.
二甲双胍（MET）被广泛用作治疗 2 型糖尿病（T2DM）的一线降血糖药物，并且已被证实对 2 型糖尿病性骨质疏松症（T2DOP）具有治疗作用。然而，MET 治疗 T2DOP 的潜在机制尚不清楚。
阐明 MET 在 T2DOP 中的作用，并探讨 MET 治疗 T2DOP 的潜在机制。
在体外，我们使用 MC3T3-E1 细胞研究了 MET 在高葡萄糖（Glucose 25 mM）环境下对成骨分化和抗氧化应激损伤的影响。在体内，我们直接使用 db/db 小鼠作为 T2DOP 模型，并通过 Micro CT 和组织学分析评估 MET 的护骨作用。
在体外，我们发现 MET 在高葡萄糖环境中增加了 MC3T3-E1 细胞中的碱性磷酸酶（ALP）活性，促进了骨矿化结节的形成，并上调了成骨相关转录因子 RUNX2、Osterix 和 COL1A1 相关基因的表达。此外，MET 能够减少高葡萄糖诱导的活性氧（ROS）产生。在对潜在机制的研究中，我们发现 MET 激活了 Nrf2/HO-1 信号通路，并减轻了高葡萄糖诱导的氧化应激损伤。体内结果表明，MET 减少了 db/db 小鼠的骨丢失和骨微结构破坏。
我们的结果表明，MET 可以激活 Nrf2/HO-1 信号通路，调节高葡萄糖诱导的成骨分化抑制，从而保护 T2DOP。
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