Gastrodin alleviates glucocorticoid induced osteoporosis in rats via activating the Nrf2 signaling pathways

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Abstract

Background: Prolonged and over-dosed administration of glucocorticoids results in more bone remodeling, leading to glucocorticoid-induced osteoporosis, which is primarily due to dysfunction and apoptosis of osteoblasts. The present study investigated the therapeutic effect and molecular mechanism of gastrodin, a natural bioactive compound isolated from the traditional Chinese herbal agent Gastrodia elata, on osteoblastic cells in vivo and in vitro. Materials and 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 DEXinduced 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 glucocorticoidinduced osteoporosis in rats by protecting osteoblasts via the Nrf2 regulated mitochondrial and ER stress-related signaling pathways.

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Liu, S., Zhou, L., Yang, L., Mu, S., Fang, T., & Fu, Q. (2018). Gastrodin alleviates glucocorticoid induced osteoporosis in rats via activating the Nrf2 signaling pathways. Oncotarget, 9(14), 11528–11540. https://doi.org/10.18632/oncotarget.23936

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