Z-Guggulsterone attenuates glucocorticoid-induced osteoporosis through activation of Nrf2/HO-1 signaling

Abstract

AimsThe present study aims to investigate the protective effect and underlying mechanism of Z-Guggulsterone (Z-GS), an active component from myrrh, on glucocorticoid-induced osteoporosis (GIO). Main methodsGIO rats were used to simulate osteoporosis in vivo while MC3T3-E1 cells were induced to osteoblast differentiation and treated with dexamethasone to simulate osteoporosis in vitro. The rats and cells were treated with Z-GS according to the protocol. The bone mineral density, biomechanical parameters and microstructure of GIO rats were measured with appropriate devices. Cell viability of MC3T3-E1 cells were analyzed via CCK-8 assay. Bone turnover markers and oxidative stress markers were detected by ELISA, and the expressions of Nrf2 and HO-1 were assessed by western blot. siRNA-Nrf2 and siRNA-HO-1 were transfected in MC3T3-E1 cells to knockdown the expressions of Nrf2 and HO-1. Key findingsZ-GS significantly increased the body weights and bone mineral density, ameliorated the femoral biomechanical parameters and microstructure of GIO rats. Z-GS treatment also reversed DXM-induced changes of bone turnover markers and oxidative stress in rats and MC3T3-E1 cells. The expressions of Nrf2 and HO-1 were inhibited in the model group and treatment with Z-GS could markedly increase their expressions. Nrf2 or HO-1 knockdown observably abrogated the beneficial role of Z-GS on cells. SignificanceOur results demonstrated that Z-GS exerted bone protective and antioxidant stress properties through activation of Nrf2/HO-1 signaling in GIO models in vivo and in vitro. Therefore, Z-GS could be considered as a promising candidate for the treatment of GIO.