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

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Abstract

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.

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Acknowledgments

The authors thank Dong Jun, PhD, for advice and discussion. Supported in part by the National Natural Science Foundation of China (Grant numbers 81271236).

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Authors and Affiliations

  1. Department of Orthopaedic Surgery, Shanghai Changzheng Hospital, Second Military Medical University, 415 Fengyang Road, Shanghai, 200003, China

    Fangjing Chen, Yueping OuYang, Huapeng Guan, Qi Liu & Bin Ni

  2. Department of Cardiology, Children’s Hospital of Shanghai, Shanghai Jiao Tong University, Shanghai, China

    Li Zhang

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  1. Fangjing Chen
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  2. Li Zhang
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  3. Yueping OuYang
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  4. Huapeng Guan
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  5. Qi Liu
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Corresponding author

Correspondence to Bin Ni.

Additional information

Fangjing Chen and Li Zhang have contributed equally to this article.

F. Chen, L. Zhang, Y. Ouyang, H. Guan, Q. Liu and B. Ni declare that they have no conflict of interest.

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Chen, F., Zhang, L., OuYang, Y. et al. Glucocorticoid Induced Osteoblast Apoptosis by Increasing E4BP4 Expression via Up-regulation of Bim. Calcif Tissue Int 94, 640–647 (2014). https://doi.org/10.1007/s00223-014-9847-6

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  • DOI: https://doi.org/10.1007/s00223-014-9847-6

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