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

• Published in: Journal of bone and mineral metabolism Vol. 27; no. 2; pp. 140 - 148
• Main Authors: Yun, Sun-Il, Yoon, Hyung-Young, Jeong, Seon-Yong, Chung, Yoon-Sok
• Format: Journal Article
• Language: English
• Published: Japan Japan : Springer Japan 01-03-2009; Springer Japan; Springer
• Subjects: Biological and medical sciences; Bones, joints and connective tissue. Antiinflammatory agents; Diseases of the osteoarticular system; Medical sciences; Medicine; Medicine & Public Health; Metabolic Diseases; Original Article; Orthopedics; Pharmacology. Drug treatments; GSK3β; p38-MAPK; Dexamethasone; Osteoblasts; Apoptosis; Enzyme; Glycogen; Transferases; Antiinflammatory agent; Rheumatology; Activation; Glucocorticoid; Kinase; Osteoblast
• ISSN: 0914-8779; 1435-5604
• DOI: 10.1007/s00774-008-0019-5

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.