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

Abstract 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 H 2 O 2 . 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, H 2 O 2 (100 μM, control), H 2 O 2  + MAN (5 μM), H 2 O 2  + MAN (10 μM), and H 2 O 2  + MAN (20 μM). MAN can significantly decrease H 2 O 2 -induced apoptosis and elevated ROS level of MC3T3-E1 cells. The expressions of caspase-3, caspase-9 and Bax/Bcl-2 were increased with H 2 O 2 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 H 2 O 2 , 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 H 2 O 2 -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.