Upregulation of SIRT1 inhibits H2O2‑induced osteoblast apoptosis via FoxO1/β‑catenin pathway

Yao,Hanlin; Yao,Zhen; Zhang,Shaocheng; Zhang,Wenjun; Zhou,Wen

doi:10.3892/mmr.2018.8657

Upregulation of SIRT1 inhibits H2O2‑induced osteoblast apoptosis via FoxO1/β‑catenin pathway

Authors:
- Hanlin Yao
- Zhen Yao
- Shaocheng Zhang
- Wenjun Zhang
- Wen Zhou
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Affiliations: Department of Orthopaedic, The Second Affiliated Hospital of Kunming Medical University, Kunming, Yunnan 650000, P.R. China, Department of Orthopaedic, Xinchang Hospital Affiliated to Wenzhou Medical University, Hangzhou, Zhejiang 312500, P.R. China, Department of Orthopaedic, Changhai Hospital Affiliated to Second Military Medical University, Shanghai 200433, P.R. China, Department of Orthopaedic, Qingpu People's Hospital of Zhujiajue, Shanghai 201713, P.R. China, Department of Sports Science, Shanghai University of Sports, Shanghai 200433, P.R. China
Published online on: March 1, 2018 https://doi.org/10.3892/mmr.2018.8657
Pages: 6681-6690

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Abstract

Osteoporosis is a disease that significantly influences life expectancy and quality in humans. Oxidative stress may stimulate bone marrow osteoclast differentiation and inhibit osteoblast (OB) differentiation. OB proliferation and differentiation are affected by the forkhead box O (FoxO)1/β‑catenin signaling pathway. The osteogenic differentiation of mesenchymal stem cells (MSCs) may be promoted by silent information regulator type‑1 [sirtuin (SIRT)1]. However, the molecular mechanism of SIRT1 regulation of osteogenic differentiation of MSCs remains unclear, and further elucidation is needed. The present study investigated the role of SIRT1 in the FoxO1/β‑catenin signaling pathway in oxidative stress and its mechanism in the osteoblastic progenitor cell line (MC3T3‑E1). The results demonstrated that OB apoptosis and elevated oxidative stress in cells were simulated by H2O2, which was inhibited by moderate SIRT1 overexpression through reducing the oxidative stress. Further studies revealed that FOXO1 and β‑catenin pathway activity was downregulated by SIRT1 and eventually resulted in inhibition of target genes, including the proapoptotic gene B cell lymphoma‑2 interacting mediator of cell death, DNA repair gene growth arrest and DNA damage inducible protein 45 and the OB differentiation suppressor gene peroxisome proliferator activated receptor (PPAR)‑γ. Furthermore, β‑catenin and PPAR‑γ were inhibited by SIRT1. Overall, the results of the present study suggest that moderate overexpression of SIRT1 (~3‑fold of normal level) may directly or indirectly inhibit apoptosis of OBs via the FOXO1 and β‑catenin signaling pathway.

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