title: Sulforaphane reverses glucocorticoid-induced apoptosis in osteoblastic cells through regulation of the Nrf2 pathway.
abstract: Apoptosis of osteoblasts triggered by high-dose glucocorticoids (GCs) has been identified as a major cause of osteoporosis. However, the underlying molecular mechanisms accounting for this action remain elusive, which has impeded the prevention and cure of this side effect. Sulforaphane (SFP) is a naturally occurring isothiocyanate that has huge health benefits for humans. In this study, by using osteoblastic MC3T3-E1 cells as a model, we demonstrate the protective effects of SFP against dexamethasone (Dex)-induced apoptosis and elucidate the underlying molecular mechanisms. The results show that SFP could effectively inhibit the Dex-induced growth inhibition and release of lactate dehydrogenase in MC3T3-E1 cells. Treatment with Dex induced caspase-dependent apoptosis in MC3T3-E1 cells, as evidenced by an increase in the Sub-G1 phase, chromatin condensation, and deoxyribonucleic acid fragmentation, which were significantly suppressed by coincubation with SFP. Mitochondria-mediated apoptosis pathway contributed importantly to Dex-induced apoptosis, as revealed by the activation of caspase-3/-9 and subsequent cleavage of poly adenosine diphosphate ribose polymerase, which was also effectively blocked by SFP. Moreover, treatments of Dex strongly induced overproduction of reactive oxygen species and inhibited the expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and the downstream effectors HO1 and NQO1. However, cotreatment with SFP effectively reversed this action of Dex. Furthermore, silencing of Nrf2 by small interfering ribonucleic acid significantly blocked the cytoprotective effects of SFP against Dex-induced apoptosis, which suggest the important role of Nrf2 signaling pathway and cell apoptosis induced by Dex. Taken together, this study provides a novel strategy for molecular intervention against Dex-induced osteoporosis using phytochemicals.
authors: Department of Spinal Surgery, Affiliated Hospital of Guangdong Medical College, Zhanjiang, People's Republic of China.
authors: Hao
authors: H
authors: Lin
authors: Department of Spinal Surgery, Affiliated Hospital of Guangdong Medical College, Zhanjiang, People's Republic of China.
authors: Bo
authors: B
authors: Wei
authors: Department of Spinal Surgery, Affiliated Hospital of Guangdong Medical College, Zhanjiang, People's Republic of China.
authors: Guangsheng
authors: G
authors: Li
authors: Department of Spinal Surgery, Affiliated Hospital of Guangdong Medical College, Zhanjiang, People's Republic of China.
authors: Jinchang
authors: J
authors: Zheng
authors: Department of Spinal Surgery, Affiliated Hospital of Guangdong Medical College, Zhanjiang, People's Republic of China.
authors: Jiecong
authors: J
authors: Sun
authors: Laboratory Institute of Minimally Invasive Orthopedic Surgery, Affiliated Hospital of Guangdong Medical College, Zhanjiang, People's Republic of China.
authors: Jiaqi
authors: J
authors: Chu
authors: Department of Spinal Surgery, Affiliated Hospital of Guangdong Medical College, Zhanjiang, People's Republic of China.
authors: Rong
authors: R
authors: Zeng
authors: Laboratory Institute of Minimally Invasive Orthopedic Surgery, Affiliated Hospital of Guangdong Medical College, Zhanjiang, People's Republic of China.
authors: Yanru
authors: Y
authors: Niu
mesh_terms: D016475:3T3 Cells; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D020169:Caspases / Q000378:metabolism; D003907:Dexamethasone / Q000633:toxicity; D020868:Gene Silencing; D005938:Glucocorticoids / Q000633:toxicity*; D017879:Isothiocyanates / Q000494:pharmacology*; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D051379:Mice; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D051267:NF-E2-Related Factor 2 / Q000235:genetics / Q000378:metabolism; D010006:Osteoblasts / Q000187:drug effects* / Q000473:pathology; D034741:RNA, Small Interfering / Q000008:administration & dosage; D015398:Signal Transduction / Q000187:drug effects; D013454:Sulfoxides
chemical_list: D005938:Glucocorticoids; D017879:Isothiocyanates; D051267:NF-E2-Related Factor 2; D034741:RNA, Small Interfering; D013454:Sulfoxides; D003907:Dexamethasone; D007770:L-Lactate Dehydrogenase; D020169:Caspases; C016766:sulforaphane
keywords: Nrf2 pathway; apoptosis; glucocorticoid; osteoporosis; sulforaphane