Background
Prolonged and over-dosed administration of glucocorticoids
Conclusions
These findings suggest that gastrodin alleviated glucocorticoid-induced osteoporosis in rats by protecting osteoblasts via the Nrf2 regulated mitochondrial and ER stress-related signaling pathways.
Methods
The anti-dexamethasone (DEX) effects of gastrodin on primary osteoblasts were measured by cell viability, flow cytometry, and western blot analysis in vitro, and also extensively examined in a rat model in vivo.
Results
The results show that gastrodin pretreatment significantly increased osteoblast viability and alkaline phosphatase activity when exposed to DEX. Alizarin Red staining indicated more calcium deposits formed in the gastrodin pretreatment against DEX group. Gastrodin alleviated DEX-induced reactive oxygen species at both the mitochondrial and cellular levels in osteoblasts. In addition, gastrodin protected primary osteoblasts from caspase3-related apoptosis by reducing the loss in the mitochondrial membrane potential and decreasing the release of DEX-induced cytochrome-C, bax, and apoptosis inducing factor. Gastrodin also antagonized upregulated endoplasmic reticulum stress signals induced by DEX, including the expression of GRP78, CHOP, and phosphorylated eIF2α. Furthermore, gastrodin protected osteoblasts by activating the nuclear factor erythroid derived 2-related factor-2 (Nrf2) pathway. Furthermore, femoral micro-computed tomography scans and biomechanical tests revealed that gastrodin improved bone microstructure and mitigated DEX-induced deterioration in bone quality. Conclusions: These findings suggest that gastrodin alleviated glucocorticoid-induced osteoporosis in rats by protecting osteoblasts via the Nrf2 regulated mitochondrial and ER stress-related signaling pathways.