title: The effect of dexamethasone and hypoxic stress on MC3T3-E1 cells.
abstract: Osteonecrosis of the femoral head (ONFH) can be caused by a decrease in the activity or numbers of osteoblasts, a process in which apoptosis may play an essential role. We investigated the effect of dexamethasone (Dex) combined with hypoxic stress on murine osteoblastic MC3T3-E1 cells. Flow cytometry, western blot and real-time quantitative PCR analyses revealed that hypoxia significantly enhanced Dex-induced apoptosis. Further data demonstrated that both the death receptor and the mitochondria-mediated pathway were involved in Dex-induced apoptosis under hypoxic conditions. However, the death receptor pathway had only a minor effect on this process. The expression levels of Bcl-2 and Bax, which regulate the mitochondria-initiated apoptotic cascade signaling pathway, were significantly different in response to Dex and hypoxia. The mitochondrial membrane potential collapsed, and the inhibitor brain- derived neurotrophic factor (BDNF) conferred effective protection against apoptosis. In summary, the mitochondria-mediated apoptotic pathway functions in osteoblast apoptosis that is induced by Dex in a hypoxic environment, and the present study may help us to gain further insight into the molecular mechanisms of steroid-induced ONFH.
authors.affiliation: Department of Orthopedic Surgery, Shanghai Sixth People's Hospital, Shanghai Jiao Tong University, 600 Yishan Road, Shanghai 200233, China.
authors.forename: Zhen-Hong
authors.initials: ZH
authors.lastname: Zhu
authors.forename: You-Shui
authors.initials: YS
authors.lastname: Gao
authors.forename: Bing-Fang
authors.initials: BF
authors.lastname: Zeng
authors.forename: Chang-Qing
authors.initials: CQ
authors.lastname: Zhang
mesh_terms: D016475:3T3 Cells; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001483:Base Sequence; D015687:Cell Hypoxia / Q000502:physiology; D045304:Cytochromes c / Q000378:metabolism; D017931:DNA Primers / Q000235:genetics; D003907:Dexamethasone / Q000494:pharmacology*; D005271:Femur Head Necrosis / Q000209:etiology / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D019254:Genes, bcl-2; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D051379:Mice; D008954:Models, Biological; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000235:genetics / Q000378:metabolism
chemical_list: C494827:Bax protein, mouse; D017931:DNA Primers; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D051028:bcl-2-Associated X Protein; D003907:Dexamethasone; D045304:Cytochromes c