Geniposide ameliorated dexamethasone-induced endoplasmic reticulum stress and mitochondrial apoptosis in osteoblasts

Eucommia ulmoides Oliver has been traditionally used for treatment of various diseases, including osteoporosis, knee pain, and paralysis. The extract of Eucommia ulmoides has been reported to stimulate the bone formation and suppress the bone resorption, leading to protection against osteoporosis (OP). Geniposide (GEN) has been considered as one of the effective compounds responsible for the therapeutic efficacy of Eucommia ulmoides against OP.To explore whether GEN protected against dexamethasone (DEX)-induced osteoporosis (OP) by activating NRF2 expression and inhibiting endoplasmic reticulum (ER) stress.The DEX-induced rat OP models were duplicated. The pathological changes were examined by histological/immunohistochemical evaluation and micro-computed tomography (micro-CT) assessment. Apoptosis was detected by a flow cytometer. Mitochondrial Ca2+ concentrations and mitochondrial membrane potential were detected. Western blot assays were used to detect the protein expression.GEN effectively reversed DEX-induced pathological changes of trabecular bone in rats. In addition, the DEX-increased expression of ATF4/CHOP was also ameliorated. In MC3T3-E1 cells, DEX promoted endoplasmic reticulum (ER) stress and mitochondrial apoptosis. Inhibition of ER stress abolished the induction of apoptosis by DEX. Similarly, GEN significantly ameliorated DEX-induced mitochondrial apoptosis. The possible underlying mechanism might be associated with the pharmacological effects of GEN on activating the expression of NRF2 and alleviating ER stress in DEX-treated MC3T3-E1 cells.GEN ameliorated DEX-induced ER stress and mitochondrial apoptosis in osteoblasts.