Glucocorticoid Induced Osteoblast Apoptosis by Increasing E4BP4 Expression via Up-regulation of Bim

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• 作者：Fangjing Chen (1)
  Li Zhang (2)
  Yueping OuYang (1)
  Huapeng Guan (1)
  Qi Liu (1)
  Bin Ni (1)
  
• 关键词：E4BP4 ; Glucocorticoid ; Osteoblasts ; Osteoporosis
• 刊名：Calcified Tissue International
• 出版年：2014
• 出版时间：June 2014
• 年：2014
• 卷：94
• 期：6
• 页码：640-647
• 全文大小：
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• 作者单位：Fangjing Chen (1)
  Li Zhang (2)
  Yueping OuYang (1)
  Huapeng Guan (1)
  Qi Liu (1)
  Bin Ni (1)
  
  1. Department of Orthopaedic Surgery, Shanghai Changzheng Hospital, Second Military Medical University, 415 Fengyang Road, Shanghai, 200003, China
  2. Department of Cardiology, Children鈥檚 Hospital of Shanghai, Shanghai Jiao Tong University, Shanghai, China
  
• ISSN：1432-0827

文摘

It is well known that glucocorticoid (GC)-induced bone loss is caused primarily by hypofunction and apoptosis of osteoblasts. However, the precise molecular events underlying the effect of GC on osteoblast apoptosis are not fully understood. Recent studies implicated an important role of E4BP4 in the regulation of osteoblast apoptosis and differentiation. Furthermore, E4BP4 is a GC-regulated gene required for GC-induced apoptosis in many cells. Therefore, we hypothesize that E4BP4 may be implicated in the process of GC-induced osteoblast apoptosis. Western blot, reverse-transcription-PCR, flow cytometry, and Hoechst 33258 staining were employed to investigate the role of E4BP4 in dexamethasone (DEX)-induced osteoblast apoptosis. We found that the expression of E4BP4 is significantly up-regulated in osteoblasts exposed to DEX. Furthermore, the depletion of E4BP4 significantly decreased DEX-induced osteoblast apoptosis. In addition, E4BP4 plays a crucial role in GC-evoked apoptosis of osteoblasts by enabling induction of Bim. On the basis of these results above, we can draw the conclusion that E4BP4 may contribute to the process of DEX-induced osteoblast apoptosis.