Mangiferin inhibits apoptosis and oxidative stress via BMP2/Smad-1 signaling in dexamethasone-induced MC3T3-E1 cells

Ding,Ling-Zhi; Teng,Xiao; Zhang,Zhao-Bo; Zheng,Chang-Jun; Chen,Shi-Hong

doi:10.3892/ijmm.2018.3506

Mangiferin inhibits apoptosis and oxidative stress via BMP2/Smad-1 signaling in dexamethasone-induced MC3T3-E1 cells

Authors:
- Ling-Zhi Ding
- Xiao Teng
- Zhao-Bo Zhang
- Chang-Jun Zheng
- Shi-Hong Chen
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Affiliations: Department of Orthopedics, Taizhou Central Hospital, Taizhou, Zhejiang 318000, P.R. China
Published online on: February 20, 2018 https://doi.org/10.3892/ijmm.2018.3506
Pages: 2517-2526
Copyright: © Ding et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Mangiferin is a xanthone glucoside, which possesses antioxidant, antiviral, antitumor and anti-inflammatory functions, and is associated with gene regulation. However, it remains unknown whether mangiferin protects osteoblasts, such as the MC3T3-E1 cell line, against glucocorticoid-induced damage. In the present study, MC3T3-E1 cells were treated with dexamethasone (Dex), which is a well-known synthetic glucocorticoid, in order to establish a glucocorticoid-induced cell injury model. After Dex and/or mangiferin treatment, cell viability, apoptosis and reactive oxygen species (ROS) production was measured by Cell Counting kit-8 (CCK-8) and flow cytometry, respectively, and the concentration of tumor necrosis factor (TNF)-α, interleukin (IL)-6 and macrophage colony-stimulating factor (M-CSF) was measured by ELISA. The expression of bone morphogenetic protein 2 (BMP2), phosphorylated‑SMAD family member 1 (p-Smad-1), t-Smad-1, osterix (OSX), osteocalcin (OCN), osteoprotegerin (OPG), receptor activator of nuclear factor-κB (RANK), RANK ligand (RANKL), B‑cell lymphoma 2 (Bcl-2) and Bcl‑2‑associated X protein (Bax) was measured by real-time PCR and/or western blot analysis. The results indicated that pretreatment of MC3T3-E1 cells with mangiferin for 3 h prior to exposure to Dex for 48 h significantly attenuated Dex-induced injury and inflammation, as demonstrated by increased cell viability, and decreases in apoptosis, ROS generation, and the secretion of TNF-α, IL-6 and M-CSF. In addition, pretreatment with mangiferin markedly reduced Dex-induced BMP2 and p‑Smad-1 downregulation, and corrected the expression of differentiation‑ and apoptosis‑associated markers, including alkaline phosphatase, OSX, OCN, OPG, RANK, RANKL, Bcl-2 and Bax, which were altered by Dex treatment. Similar to the protective effects of mangiferin, overexpression of BMP2 suppressed not only Dex-induced cytotoxicity, but also ROS generation, and the secretion of TNF-α, IL-6 and M-CSF. In conclusion, the results of the present study are the first, to the best of our knowledge, to demonstrate that mangiferin protects MC3T3-E1 cells against Dex-induced apoptosis and oxidative stress by activating the BMP2/Smad-1 signaling pathway.

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