Geniposide attenuates cadmium‑induced oxidative stress injury via Nrf2 signaling in osteoblasts.

Abstract

Geniposide, as a type of iridoid glycoside, has antioxidative capacity. However, the mechanism underlying the effect of geniposide in cadmium (Cd)-induced osteoblast injury remains only partly elucidated. In the present study, Cell Counting Kit-8 (CCK-8) was used to determine MC-3T3-E1 cell viability. Flow cytometry was used to determine the rate of apoptosis and levels of reactive oxygen species (ROS). Oxidative stress-related factors were assessed using enzyme-linked immunosorbent method (ELISA). Quantitative real-time polymerase chain reaction (qPCR) and western blotting were used to evaluate apoptosis- and bone formation-related genes and nuclear factor erythroid 2-related factor (Nrf2) signaling. It was demonstrated that geniposide increased the viability of the Cd-treated MC-3T3-E1 cells. Geniposide decreased apoptosis and ROS accumulation compared to these parameters in the Cd group. Geniposide attenuated oxidative stress-related factors, malondialdehyde and lactate dehydrogenase and increased antioxidant key enzyme superoxidase dismutase (SOD). The expression levels of Bax, Bcl-2 and survivin were modulated by geniposide. Additionally, the mRNA and protein expression of the receptor activator of NF-κB ligand (RANKL) and osterix were significantly increased, while osteoprotegerin was decreased by geniposide treatment compared to the Cd groups. Geniposide also enhanced Nrf2, heme oxygenase-1 (HO-1) and NAD(P)H quinone dehydrogenase 1 (NQO1) expression. The present study identified a potential agent for the treatment of Cd-induced osteoblast injury.