PMID- 29393365 OWN - NLM STAT- MEDLINE DCOM- 20180829 LR - 20181113 IS - 1791-244X (Electronic) IS - 1107-3756 (Print) IS - 1107-3756 (Linking) VI - 41 IP - 4 DP - 2018 Apr TI - Gastrodin protects MC3T3-E1 osteoblasts from dexamethasone-induced cellular dysfunction and promotes bone formation via induction of the NRF2 signaling pathway. PG - 2059-2069 LID - 10.3892/ijmm.2018.3414 [doi] AB - Glucocorticoid (GC)-induced osteoporosis (GIO) is one of the most common secondary and iatrogenic forms of osteoporosis. GCs are widely used in clinical therapy and play a key role in the normal regulation of bone remodeling. However, the prolonged and high-dose administration of GCs results in the occurrence of osteoporosis, which is partially due to the dysfunction and apoptosis of osteoblasts and osteocytes. The aim of the present study was to investigate the effects of gastrodin, a natural bioactive compound isolated from the traditional Chinese herbal agent Gastrodia elata, on GC-treated MC3T3‑E1 murine osteoblastic cells. MC3T3‑E1 cells were exposed to dexamethasone (DEX), with or without gastrodin pretreatment, and cell viability was measured by the cell counting kit-8 (CCK-8) assay. Quantitative polymerase chain reaction analysis was performed to evaluate osteogenic gene expression, and cellular alkaline phosphatase (ALP) activity was measured as well. Alizarin Red staining of calcium deposits was found to reflect the degree of osteoblast maturity. Western blotting was performed to determine the expression of osteogenic and adipogenic differentiation key proteins, as well as nuclear factor-like 2 (NRF2) pathway‑related proteins. Annexin V-fluorescein isothiocyanate̸propidium iodide flow cytometric analysis was performed to determine osteoblast apoptosis. JC-1 staining was used to detect the changes of the mitochondrial membrane potential in cells. The results revealed that gastrodin prevented the decrease in cell viability caused by DEX-induced MC3T3‑E1 cell dysfunction, and that groups pretreated with gastrodin exhibited higher mRNA levels of osteogenic genes, such as Runx2, osterix, bone morphogenetic protein-2 and osteocalcin. Furthermore, treatment with both DEX and gastrodin was associated with increased ALP activity in MC3T3-E1 cells, as well as more calcium deposits, compared with cells treated with DEX alone. In addition, gastrodin increased osteogenic key marker protein Runx2 while activating NRF2 and downstream effector protein expression. Therefore, gastrodin may have the potential to reduce DEX-induced cell apoptosis and increase the mitochondrial membrane potential against DEX. These results demonstrated that gastrodin was able to prevent and/or delay DEX‑induced osteoporosis by improving osteoblast function, and these protective effects were verified in an animal model. FAU - Liu, Shengye AU - Liu S AD - Department of Spine and Joint Surgery, The Shengjing Hospital of China Medical University, Shenyang, Liaoning 110004, P.R. China. FAU - Fang, Tao AU - Fang T AD - Department of Spine and Joint Surgery, The Shengjing Hospital of China Medical University, Shenyang, Liaoning 110004, P.R. China. FAU - Yang, Liyu AU - Yang L AD - Department of Spine and Joint Surgery, The Shengjing Hospital of China Medical University, Shenyang, Liaoning 110004, P.R. China. FAU - Chen, Zhiguang AU - Chen Z AD - Emergency Department, The Shengjing Hospital of China Medical University, Shenyang, Liaoning 110004, P.R. China. FAU - Mu, Shuai AU - Mu S AD - Department of Spine and Joint Surgery, The Shengjing Hospital of China Medical University, Shenyang, Liaoning 110004, P.R. China. FAU - Fu, Qin AU - Fu Q AD - Department of Spine and Joint Surgery, The Shengjing Hospital of China Medical University, Shenyang, Liaoning 110004, P.R. China. LA - eng PT - Journal Article DEP - 20180123 PL - Greece TA - Int J Mol Med JT - International journal of molecular medicine JID - 9810955 RN - 0 (Benzyl Alcohols) RN - 0 (Drugs, Chinese Herbal) RN - 0 (Glucocorticoids) RN - 0 (Glucosides) RN - 0 (NF-E2-Related Factor 2) RN - 0 (Nfe2l2 protein, mouse) RN - 0 (Protective Agents) RN - 5YS9U2W3RQ (gastrodin) RN - 7S5I7G3JQL (Dexamethasone) SB - IM MH - Animals MH - Benzyl Alcohols/chemistry/*pharmacology/therapeutic use MH - Cell Line MH - Dexamethasone/*adverse effects MH - Drugs, Chinese Herbal/chemistry/pharmacology/therapeutic use MH - Female MH - Gastrodia/chemistry MH - Glucocorticoids/*adverse effects MH - Glucosides/chemistry/*pharmacology/therapeutic use MH - Mice MH - NF-E2-Related Factor 2/*metabolism MH - Osteoblasts/*drug effects/metabolism/pathology MH - Osteogenesis/*drug effects MH - Osteoporosis/chemically induced/metabolism/pathology/prevention & control MH - Protective Agents/chemistry/*pharmacology/therapeutic use MH - Rats, Sprague-Dawley MH - Signal Transduction/drug effects PMC - PMC5810206 COIS- Competing interests The authors declare that they have no competing interests. EDAT- 2018/02/03 06:00 MHDA- 2018/08/30 06:00 PMCR- 2018/01/23 CRDT- 2018/02/03 06:00 PHST- 2016/11/02 00:00 [received] PHST- 2018/01/09 00:00 [accepted] PHST- 2018/02/03 06:00 [pubmed] PHST- 2018/08/30 06:00 [medline] PHST- 2018/02/03 06:00 [entrez] PHST- 2018/01/23 00:00 [pmc-release] AID - ijmm-41-04-2059 [pii] AID - 10.3892/ijmm.2018.3414 [doi] PST - ppublish SO - Int J Mol Med. 2018 Apr;41(4):2059-2069. doi: 10.3892/ijmm.2018.3414. Epub 2018 Jan 23.