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.