The effect of dexamethasone and hypoxic stress on MC3T3-E1 cells

Front Biosci (Landmark Ed). 2011 Jun 1;16:2747-55. doi: 10.2741/3883.

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.

MeSH terms

  • 3T3 Cells
  • Animals
  • Apoptosis / drug effects
  • Base Sequence
  • Cell Hypoxia / physiology
  • Cytochromes c / metabolism
  • DNA Primers / genetics
  • Dexamethasone / pharmacology*
  • Femur Head Necrosis / etiology
  • Femur Head Necrosis / genetics
  • Femur Head Necrosis / metabolism
  • Femur Head Necrosis / pathology
  • Genes, bcl-2
  • Membrane Potential, Mitochondrial / drug effects
  • Mice
  • Models, Biological
  • Osteoblasts / cytology
  • Osteoblasts / drug effects*
  • Osteoblasts / metabolism*
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • bcl-2-Associated X Protein / genetics
  • bcl-2-Associated X Protein / metabolism

Substances

  • Bax protein, mouse
  • DNA Primers
  • Proto-Oncogene Proteins c-bcl-2
  • RNA, Messenger
  • bcl-2-Associated X Protein
  • Dexamethasone
  • Cytochromes c