文章基本信息

标题：Haem oxygenase-1 induction prevents glucocorticoid-induced osteoblast apoptosis through activation of extracellular signal–regulated kinase1/2 signalling pathway
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作者：Qiaoli Gu ; Mimi Chen ; Yu Zhang 等
期刊名称：Journal of Orthopaedic Translation
印刷版ISSN：2214-031X
出版年度：2019
卷号：19
页码：29-37
DOI：10.1016/j.jot.2019.04.003
出版社：Elsevier B.V.
摘要：Background High-dose glucocorticoid (GC) therapy always causes osteoporosis partly by inducing osteoblast apoptosis. However, the underlying mechanisms of GC-induced apoptosis remain elusive. Haem oxygenase-1 (HO-1) is a cytoprotective protein that rescues cells from H₂O₂ or high glucose–induced apoptosis. In bone metabolism, HO-1 also participates in osteoclast and osteoblast differentiation. Objective The present study aimed to investigate the protective role of HO-1 against GC-induced osteoblast apoptosis and to elucidate the underlying mechanism. Methods Mouse osteoblastic MC3T3-E1 cells were treated with dexamethasone (Dex) for 24 h in the presence or absence of cobalt (III) protoporphyrin IX chloride (CoPP, an inducer of HO-1). In some experiments, U0126 was added to the culture 1 h before CoPP treatment. The induction of apoptosis was determined by flow cytometry. Cell viability was evaluated using a cell counting kit-8 (CCK-8) assay. The expression levels of Bax and bcl-2 were measured by real-time polymerase chain reaction and Western blot. HO-1, extracellular signal–regulated kinase (ERK)-1/2 and pERK1/2 protein levels were measured by Western blot analysis. Results Dex promoted apoptosis and inhibited cell viability in MC3T3-E1 cells. In addition, Dex significantly increased Bax expression and reduced Bcl-2 expression. The expression of HO-1 was also reduced after Dex treatment. HO-1 induction by CoPP significantly attenuated Dex-induced apoptosis as evidenced by Annexin V/PI staining. The mRNA expression level of antiapoptotic gene Bcl-2 was also increased after CoPP treatment. Moreover, CoPP treatment increased the phosphorylation of ERK1/2. U0126, an inhibitor of ERK activation, significantly abrogated the protective effects of CoPP. Conclusion Our results demonstrate that HO-1 induction by CoPP can attenuate Dex-induced apoptosis of mouse osteoblastic MC3T3-E1 cells. The antiapoptotic effect of HO-1 induction may be correlated with the activation of ERK1/2 signalling pathway. The translational potential of this article: HO-1 induction by CoPP can prevent GC-induced osteoblast apoptosis. Our findings will highlight the therapeutic potential of HO-1 induction in GC-induced osteoporosis.
关键词：Apoptosis ; Glucocorticoid ; Haem oxygenase-1 ; Osteoblast