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Hyperhomocysteinemia inhibits tibial fracture healing in rats through PI3K/AKT signaling pathway

  • Authors:
    • Su Liu
    • Yunzong Huang
    • Shoujing Tian
    • Wei Zhang
    • Youjia Xu
    • Jianfei Ge
  • View Affiliations / Copyright

    Affiliations: Department of Orthopedics, The Affiliated Zhangjiagang Hospital of Soochow University, Zhangjiagang, Jiangsu 215600, P.R. China, Department of Orthopedics, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215004, P.R. China
    Copyright: © Liu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 2083-2088
    |
    Published online on: January 3, 2020
       https://doi.org/10.3892/etm.2020.8412
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Abstract

To explore the influence of hyperhomocysteinemia (hHcys) on the tibial fracture healing in rats and its effect on the phosphatidylinositol 3‑hydroxy kinase (PI3K)/protein kinase B (AKT) signaling pathway. A total of 36 Sprague‑Dawley rats were randomly divided into sham group (n=12), tibial fracture group (n=12) and hHcys + fracture group (n=12). The rats in tibial fracture group underwent the tibial fracture surgery, while the model of tibial fracture and hHcys was established in hHcys + fracture group. The level of plasma homocysteine (Hcy) in each group was analyzed using the full‑automatic biochemical analyzer, the fracture stress biomechanical measurement was performed, and the ultimate bending strength and torque were calculated. Moreover, the protein expressions of PI3K and phosphorylated (p)‑AKT in tibial tissues were detected using western blotting, the messenger ribonucleic acid (mRNA) levels of Bcl‑2 associated X protein (Bax) and caspase‑3 were detected using quantitative polymerase chain reaction (qPCR), the apoptosis was detected via terminal deoxynucleotidyl transferase‑mediated dUTP nick end labeling (TUNEL) staining, and the expressions of inflammatory factors were detected via immunohistochemistry. Compared with sham group, tibial fracture group and hHcys + fracture group had a significantly increased level of plasma Hcy, significantly decreased ultimate bending strength and torque, obviously decreased relative protein expressions of PI3K and p‑AKT, increased mRNA levels of Bax and caspase‑3 and an increased expression of pro‑inflammatory factor tumor necrosis factor‑α (TNF‑α). Compared with tibial fracture group, hHcys + fracture group had a higher level of plasma Hcy, lower ultimate bending strength and torque, lower relative protein expressions of PI3K and p‑AKT, higher mRNA levels of Bax and caspase‑3, a higher apoptosis rate and a higher expression of TNF‑α. hHcys blocks the downstream apoptotic signal transduction, promotes apoptosis and inflammatory response, and affects fracture healing through ​​affecting the PI3K/AKT signaling pathway.
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Copy and paste a formatted citation
Spandidos Publications style
Liu S, Huang Y, Tian S, Zhang W, Xu Y and Ge J: Hyperhomocysteinemia inhibits tibial fracture healing in rats through PI3K/AKT signaling pathway. Exp Ther Med 19: 2083-2088, 2020.
APA
Liu, S., Huang, Y., Tian, S., Zhang, W., Xu, Y., & Ge, J. (2020). Hyperhomocysteinemia inhibits tibial fracture healing in rats through PI3K/AKT signaling pathway. Experimental and Therapeutic Medicine, 19, 2083-2088. https://doi.org/10.3892/etm.2020.8412
MLA
Liu, S., Huang, Y., Tian, S., Zhang, W., Xu, Y., Ge, J."Hyperhomocysteinemia inhibits tibial fracture healing in rats through PI3K/AKT signaling pathway". Experimental and Therapeutic Medicine 19.3 (2020): 2083-2088.
Chicago
Liu, S., Huang, Y., Tian, S., Zhang, W., Xu, Y., Ge, J."Hyperhomocysteinemia inhibits tibial fracture healing in rats through PI3K/AKT signaling pathway". Experimental and Therapeutic Medicine 19, no. 3 (2020): 2083-2088. https://doi.org/10.3892/etm.2020.8412
Copy and paste a formatted citation
x
Spandidos Publications style
Liu S, Huang Y, Tian S, Zhang W, Xu Y and Ge J: Hyperhomocysteinemia inhibits tibial fracture healing in rats through PI3K/AKT signaling pathway. Exp Ther Med 19: 2083-2088, 2020.
APA
Liu, S., Huang, Y., Tian, S., Zhang, W., Xu, Y., & Ge, J. (2020). Hyperhomocysteinemia inhibits tibial fracture healing in rats through PI3K/AKT signaling pathway. Experimental and Therapeutic Medicine, 19, 2083-2088. https://doi.org/10.3892/etm.2020.8412
MLA
Liu, S., Huang, Y., Tian, S., Zhang, W., Xu, Y., Ge, J."Hyperhomocysteinemia inhibits tibial fracture healing in rats through PI3K/AKT signaling pathway". Experimental and Therapeutic Medicine 19.3 (2020): 2083-2088.
Chicago
Liu, S., Huang, Y., Tian, S., Zhang, W., Xu, Y., Ge, J."Hyperhomocysteinemia inhibits tibial fracture healing in rats through PI3K/AKT signaling pathway". Experimental and Therapeutic Medicine 19, no. 3 (2020): 2083-2088. https://doi.org/10.3892/etm.2020.8412
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