Ursolic acid protects MC3T3-E1 cells against dexamethasone-mediated apoptosis, ROS generation and inflammation through activation of IGF-1

Ursolic acid (UA), a pentacyclic triterpenoid found in a variety of plants, has attracted considerable attention because of its important biological and pharmacological activities. However, its effect on osteoclasts and mechanism of action require further investigation. In the current study, MC3T3-E1 cells were treated with dexamethasone (DEX), a well-known synthetic glucocorticoid, to establish a glucocorticoid-induced osteoporosis model. Our findings demonstrated that treatment of MC3T3-E1 cells with DEX significantly decreased cell proliferation and expression level of insulin-like growth factor 1 (IGF-1) in a dose-dependent manner. However, pretreatment of MC3T3-E1 cells with UA before exposure to DEX significantly attenuated DEX-induced apoptosis and ROS generation and secretions of TNF-alpha and IL-6. In addition, pretreatment with UA markedly reduced DEX-induced IGF-1 downregulation. Similar to the protective effect of UA, overexpression of IGF-1 depressed not only DEX-induced cytotoxicity, but also BMP2 downregulation and decreases in ratio of OPG/RANKL and Bax/Bcl-2. Taken together, the findings of the present study have demonstrated for the first time that UA protects MC3T3-E1 cells against DEX-induced apoptosis, oxidative stress and inflammation through activating IGF-1.