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Metformin promotes cell proliferation and osteogenesis under high glucose condition by regulating the ROS‑AKT‑mTOR axis

  • Authors:
    • Renyi Zhou
    • Yue Ma
    • Shui Qiu
    • Zunlei Gong
    • Xiaoshu Zhou
  • View Affiliations / Copyright

    Affiliations: Department of Orthopedics, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning 110001, P.R. China, Department of Respiratory and Critical Care Medicine, Shengjing Hospital of China Medical University, Shenyang, Liaoning 110001, P.R. China
    Copyright: © Zhou et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 3387-3395
    |
    Published online on: July 30, 2020
       https://doi.org/10.3892/mmr.2020.11391
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Abstract

Metformin, a cost‑effective and safe orally administered antidiabetic drug used by millions of patients, has exhibited great interest for its potential osteogenic‑promoting properties in different types of cells, including mesenchymal stem cells (MSCs). Diabetic osteopathy is a common comorbidity of diabetes mellitus; however, the underlying molecular mechanisms of metformin on the physiological processes of MSCs, under high glucose condition, remain unknown. To determine the effects of metformin on the regulatory roles of proliferation and differentiation in MSCs, under high glucose conditions, osteogenesis after metformin treatment was detected with Alizarin Red S and ALP staining. The results demonstrated that high glucose levels significantly inhibited cell proliferation and osteogenic differentiation under high glucose conditions. Notably, addition of metformin reversed the inhibitory effects induced by high glucose levels on cell proliferation and osteogenesis. Furthermore, high glucose levels significantly decreased mitochondrial membrane potential (MMP), whereas treatment with metformin helped maintain MMP. Further analysis of mitochondrial function revealed that metformin significantly promoted ATP synthesis, mitochondrial DNA mass and mitochondrial transcriptional activity, which were inhibited by high glucose culture. Furthermore, metformin significantly scavenged reactive oxygen species (ROS) induced by high glucose levels, and regulated the ROS‑AKT‑mTOR axis inhibited by high glucose levels, suggesting the protective effects of metformin against high glucose levels via regulation of the ROS‑AKT‑mTOR axis. Taken together, the results of the present study demonstrated the protective role of metformin on the physiological processes of MSCs, under high glucose condition and highlighted the potential molecular mechanism underlying the effect of metformin in promoting cell proliferation and osteogenesis under high glucose condition.
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Copy and paste a formatted citation
Spandidos Publications style
Zhou R, Ma Y, Qiu S, Gong Z and Zhou X: Metformin promotes cell proliferation and osteogenesis under high glucose condition by regulating the ROS‑AKT‑mTOR axis. Mol Med Rep 22: 3387-3395, 2020.
APA
Zhou, R., Ma, Y., Qiu, S., Gong, Z., & Zhou, X. (2020). Metformin promotes cell proliferation and osteogenesis under high glucose condition by regulating the ROS‑AKT‑mTOR axis. Molecular Medicine Reports, 22, 3387-3395. https://doi.org/10.3892/mmr.2020.11391
MLA
Zhou, R., Ma, Y., Qiu, S., Gong, Z., Zhou, X."Metformin promotes cell proliferation and osteogenesis under high glucose condition by regulating the ROS‑AKT‑mTOR axis". Molecular Medicine Reports 22.4 (2020): 3387-3395.
Chicago
Zhou, R., Ma, Y., Qiu, S., Gong, Z., Zhou, X."Metformin promotes cell proliferation and osteogenesis under high glucose condition by regulating the ROS‑AKT‑mTOR axis". Molecular Medicine Reports 22, no. 4 (2020): 3387-3395. https://doi.org/10.3892/mmr.2020.11391
Copy and paste a formatted citation
x
Spandidos Publications style
Zhou R, Ma Y, Qiu S, Gong Z and Zhou X: Metformin promotes cell proliferation and osteogenesis under high glucose condition by regulating the ROS‑AKT‑mTOR axis. Mol Med Rep 22: 3387-3395, 2020.
APA
Zhou, R., Ma, Y., Qiu, S., Gong, Z., & Zhou, X. (2020). Metformin promotes cell proliferation and osteogenesis under high glucose condition by regulating the ROS‑AKT‑mTOR axis. Molecular Medicine Reports, 22, 3387-3395. https://doi.org/10.3892/mmr.2020.11391
MLA
Zhou, R., Ma, Y., Qiu, S., Gong, Z., Zhou, X."Metformin promotes cell proliferation and osteogenesis under high glucose condition by regulating the ROS‑AKT‑mTOR axis". Molecular Medicine Reports 22.4 (2020): 3387-3395.
Chicago
Zhou, R., Ma, Y., Qiu, S., Gong, Z., Zhou, X."Metformin promotes cell proliferation and osteogenesis under high glucose condition by regulating the ROS‑AKT‑mTOR axis". Molecular Medicine Reports 22, no. 4 (2020): 3387-3395. https://doi.org/10.3892/mmr.2020.11391
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