Metformin attenuates H<sub>2</sub>O<sub>2</sub>‑induced osteoblast apoptosis by regulating SIRT3 via the PI3K/AKT pathway

Yang,Keda; Pei,Lei; Zhou,Siming; Tao,Lin; Zhu,Yue

doi:10.3892/etm.2021.10751

Metformin attenuates H₂O₂‑induced osteoblast apoptosis by regulating SIRT3 via the PI3K/AKT pathway

Authors:
- Keda Yang
- Lei Pei
- Siming Zhou
- Lin Tao
- Yue Zhu
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Affiliations: Department of Orthopedics, First Hospital of China Medical University, Shenyang, Liaoning 110001, P.R. China
Published online on: September 17, 2021 https://doi.org/10.3892/etm.2021.10751
Article Number: 1316
Copyright: © Yang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Osteoporosis is a common metabolic disease that has a high incidence in postmenopausal women. Studies have indicated that oxidative damage plays an important role in the development of postmenopausal osteoporosis. Metformin has been showed to have the ability to relieve excessive oxidation. The aim of the present was to determine the therapeutic effect and potential mechanism of metformin in postmenopausal osteoporosis. Oxidative damage was stimulated in vitro by the addition of H₂O₂ to MC3T3‑E1 cells and a mouse menopausal model was also constructed. Cell viability and flow cytometry experiments were performed to determine the effects of H₂O₂ and metformin treatment on apoptosis. Mitochondrial membrane potential was tested by JC‑1 assays. Western blotting was used to detect the expression of mitochondrial apoptosis markers and antioxidant enzymes. Small interfering RNA was used to knockdown sirtuin3 (SIRT3), which was verified at the mRNA and protein levels. Bilateral ovariectomy was used to prepare menopausal mice, which were analyzed using micro‑computed tomography. The results indicated that metformin is able to repair mitochondrial damage and inhibit the apoptosis of osteoblasts induced by H₂O₂, and also reverse bone mass loss in ovariectomized mice. Western blotting results demonstrated the involvement of SIRT3 in the production of antioxidant enzymes that are essential in protecting against mitochondrial injury. In addition, experiments with SIRT3 knockdown indicated that metformin reverses H₂O₂‑induced osteoblast apoptosis by upregulating the expression of SIRT3 via the PI3K/AKT pathway. The results of the present reveal the pathogenesis of oxidative damage and the therapeutic effect of metformin in postmenopausal osteoporosis. They also suggest that SIRT3 is a potential drug target in the treatment of osteoporosis, with metformin being a candidate drug for modification and/or clinical application.

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