Journal of Bone and Mineral Metabolism

, Volume 27, Issue 2, pp 140–148

Glucocorticoid induces apoptosis of osteoblast cells through the activation of glycogen synthase kinase 3β

  • Sun-Il Yun
  • Hyung-Young Yoon
  • Seon-Yong Jeong
  • Yoon-Sok Chung
Original Article

DOI: 10.1007/s00774-008-0019-5

Cite this article as:
Yun, SI., Yoon, HY., Jeong, SY. et al. J Bone Miner Metab (2009) 27: 140. doi:10.1007/s00774-008-0019-5
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Abstract

Glucocorticoids (GCs), which play an important role in the normal regulation of bone remodeling, are widely used as anti-inflammatory and chemotherapeutic agents. However, continued exposure to GCs results in osteoporosis, which is partially due to apoptosis of osteoblasts and osteocytes. To understand the mechanism of how GCs induce cell death in osteoblasts, we examined apoptotic effects of dexamethasone (Dex), GC, on MC3T3-E1 osteoblast cells. Results revealed that Dex-induced apoptosis was inhibited by a GC receptor antagonist, mifepristone, and a general caspase inhibitor, Z-VAD-fmk, indicating that Dex induces apoptosis of MC3T3-E1 cells through the pathways involved in GC receptor and caspase. Glycogen synthase kinase 3β (GSK3β) is known to participate in apoptosis signaling in MC3T3-E1 cells. Dex activated both GSK3β and p38-mitogen-activated protein kinase (MAPK). The inhibition of GSK3β by inhibitor (LiCl) or small interference RNA (siRNA) decreased apoptosis. In contrast, the inhibition of p38-MAPK by inhibitor (SB203580) or siRNA did not decrease, but increase apoptosis. These results suggest that Dex-mediated apoptosis of osteoblasts is facilitated by GSK3β, but prevented by p38-MAPK.

Keywords

DexamethasoneOsteoblastsApoptosisGSK3βp38-MAPK

Copyright information

© The Japanese Society for Bone and Mineral Research and Springer 2008

Authors and Affiliations

  • Sun-Il Yun
    • 1
  • Hyung-Young Yoon
    • 1
  • Seon-Yong Jeong
    • 2
  • Yoon-Sok Chung
    • 1
  1. 1.Department of Endocrinology and MetabolismAjou University School of MedicineSuwon CitySouth Korea
  2. 2.Department of Medical GeneticsAjou University School of MedicineSuwon CitySouth Korea