Mangiferin protects osteoblast against oxidative damage by modulation of ERK5/Nrf2 signaling.

Oxidative stress has currently been proposed as a risk factor associated with the development and proression of osteoporosis. In this study, we identify the effect of mangiferin (MAN) on apoptosis and differentiation of osteoblast-like MC3T3-E1 cells insulted by HO. We firstly found that MAN can promote cell proliferation of MC3T3-E1 cells in a time- and dose-dependent manner and stimulate the phosphorylation of ERK5. Cells were divided as five groups: control, HO (100 μM, control), HO + MAN (5 μM), HO + MAN (10 μM), and HO + MAN (20 μM). MAN can significantly decrease HO-induced apoptosis and elevated ROS level of MC3T3-E1 cells. The expressions of caspase-3, caspase-9 and Bax/Bcl-2 were increased with HO treatment, and MAN can reverse these changes. In addition, Nrf2 and its downstream target effectors (HO1, NQO1) were dramatically attenuated in MC3T3-E cells treatment with HO, while MAN can significantly increase the expression of Nrf2, HO1 and NQO1. The expression of ERK5 was down regulated by RNA interference in MC3T3-E1 cells, and we found that MAN (20 μM) pretreatment didn't make remarkable decrease in cell apoptosis or expressions of apoptosis-related proteins in HO-insulted siRNA-ERK5 cells. This study indicated that MAN can protect osteoblast against oxidative damage by modulation of ERK5/Nrf2 signaling, which can be new agent for osteoporosis.