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

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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.

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Acknowledgment

This research was supported by the “GRRC” Project of Gyeonggi Provincial Government, Republic of Korea.

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Authors and Affiliations

  1. Department of Endocrinology and Metabolism, Ajou University School of Medicine, San 5 Wonchon-Dong Yeongtong-Gu, Suwon City, Gyeonggi Province, 443-721, South Korea

    Sun-Il Yun, Hyung-Young Yoon & Yoon-Sok Chung

  2. Department of Medical Genetics, Ajou University School of Medicine, San 5 Wonchon-Dong Yeongtong-Gu, Suwon City, Gyeonggi Province, 443-721, South Korea

    Seon-Yong Jeong

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  1. Sun-Il Yun
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  2. Hyung-Young Yoon
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Correspondence to Yoon-Sok Chung.

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Yun, SI., Yoon, HY., Jeong, SY. et al. Glucocorticoid induces apoptosis of osteoblast cells through the activation of glycogen synthase kinase 3β. J Bone Miner Metab 27, 140–148 (2009). https://doi.org/10.1007/s00774-008-0019-5

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  • DOI: https://doi.org/10.1007/s00774-008-0019-5

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