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Decrease of GSK3β Ser-9 Phosphorylation Induced Osteoblast Apoptosis in Rat Osteoarthritis Model

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Abstract

Nowadays, the cumulative intake of glucocorticoids has become the most common pathogenic factor for non-traumatic osteonecrosis of the femoral head (ONFH). Apoptosis of osteoblasts is considered as the main reason of ONFH at the molecular level. Glycogen synthase kinase 3β (GSK3β) is an important regulator of cellular differentiation and apoptosis pathway, which can modulate the balance between osteoblasts and osteoclasts. Several studies have reported about its function in osteoporosis, but little is known about it in osteonecrosis. In our study, lipopolysaccharide and methylprednisolone were utilized to establish a rat ONFH model. The phosphorylation of GSK3β Ser-9 was decreased in the model. Western blotting examination of β-catenin, Bcl-2, Bax and caspase-3 revealed that the osteoblasts were apoptotic. In dexamethasone (Dex)-incubated primary osteoblasts, the expression profile of GSK3β phosphorylation and apoptotic factors were consistent with those in the rat ONFH model. To further investigate the regulation of osteonecrosis caused by GSK3β, the expression and function of GSK3β were inhibited in Dex-incubated primary osteoblasts. The knockdown of GSK3β by siRNA decreased the expression of Bax and cleaved caspase-3, but increased Bcl-2 and β-catenin. On the other hand, selective inhibition of GSK3β function by LiCl counteracted the activation of caspase-3 induced by Dex. Our work is the first study about the GSK3β phosphorylation in ONFH, and provides evidence for further therapeutic methods.

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Author notes

  1. The authors contributed equally to this article.

Authors and Affiliations

  1. Department of Orthopedics, Renmin Hospital of Wuhan University, Wuhan, 430060, China

    Shuang Deng, Zhi-gang Nie, Pu-ji Peng, Yang Liu, Sai Xing, Lin-sheng Long & Hao Peng

Authors
  1. Shuang Deng
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  2. Zhi-gang Nie
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  3. Pu-ji Peng
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  4. Yang Liu
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  5. Sai Xing
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  6. Lin-sheng Long
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  7. Hao Peng
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Corresponding author

Correspondence to Hao Peng.

Additional information

This study was supported by the National Natural Science Foundation of China (No. 81672154).

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Deng, S., Nie, Zg., Peng, Pj. et al. Decrease of GSK3β Ser-9 Phosphorylation Induced Osteoblast Apoptosis in Rat Osteoarthritis Model. CURR MED SCI 39, 75–80 (2019). https://doi.org/10.1007/s11596-019-2002-x

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  • DOI: https://doi.org/10.1007/s11596-019-2002-x

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