Low-dose dexamethasone affects osteoblast viability by inducing autophagy via intracellular ROS.

Abstract

Glucocorticoids (GCs) are closely associated with the progression of GC-induced osteoporosis (GIOP) by inhibiting osteoblast viability. However, endogenous GCs are important for bone development. In addition, previous studies have demonstrated that GCs could induce autophagy, a cytoprotective process that is protective against various stressors. In the present study, the aim is to explore whether osteoblasts exhibited dose-dependent viability in the presence of GCs due to autophagy. hFOB 1.19 osteoblasts were treated with various doses of dexamethasone (DEX; 10−8-10−4 M) for 0, 24, 48 and 72 h. The results revealed a biphasic effect of DEX on the viability of hFOB 1.19 cells; a high dose of DEX (≥10−6 M) accelerated cell apoptosis, while a low dose of DEX (10−8 M) increased cell viability. Furthermore, significantly increased autophagy was observed in the low dose DEX treatment group, as indicated by the expression of the autophagy-associated proteins beclin 1 and microtubule-associated protein light chain 3, and the detection of autophagosomes. Another finding was that DEX upregulated intracellular reactive oxygen species (ROS), which was decreased by the autophagy agonist rapamycin. The increase in autophagy and cell viability associated with low-dose DEX (10−8 M) was suppressed by the ROS scavenger catalase and the autophagy inhibitor 3-methyladenine. In conclusion, the results revealed that GCs affected osteoblast viability in a dose-dependent manner. A low dose of GCs increased osteoblast viability by inducing autophagy via intracellular ROS. The results indicate that autophagy may be a novel mechanism by which osteoblasts survive GC exposure and provide a potential therapeutic target for treating GIOP.