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

Authors
Yun, SI; Yoon, HY; Jeong, SY; Chung, YS
Citation
Journal of bone and mineral metabolism, 27(2):140-148, 2009
Journal Title
Journal of bone and mineral metabolism
ISSN
0914-87791435-5604
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 3beta (GSK3beta) is known to participate in apoptosis signaling in MC3T3-E1 cells. Dex activated both GSK3beta and p38-mitogen-activated protein kinase (MAPK). The inhibition of GSK3beta 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 GSK3beta, but prevented by p38-MAPK.
MeSH terms
AnimalsApoptosis/drug effects*Caspases/metabolismDexamethasone/pharmacology*Enzyme Activation/drug effectsGene Knockdown TechniquesGene Silencing/drug effectsGlycogen Synthase Kinase 3/metabolism*MiceOsteoblasts/cytology*Osteoblasts/drug effectsOsteoblasts/enzymology*Receptors, Glucocorticoid/metabolismp38 Mitogen-Activated Protein Kinases/metabolism
DOI
10.1007/s00774-008-0019-5
PMID
19066717
Appears in Collections:
Journal Papers > School of Medicine / Graduate School of Medicine > Endocrinology & Metabolism
Journal Papers > School of Medicine / Graduate School of Medicine > Medical Genetics
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