Drug Design, Development and Therapy (Apr 2021)

Alendronate Alleviated Femoral Head Necrosis and Upregulated BMP2/EIF2AK3/EIF2A/ATF4 Pathway in Liquid Nitrogen Treated Rats

  • Rong K,
  • Li X,
  • Jiang W,
  • Wu X,
  • Xia Q,
  • Chen J,
  • Yin X

Journal volume & issue
Vol. Volume 15
pp. 1717 – 1724

Abstract

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Ke Rong,1 Xiaoliu Li,2 Weimin Jiang,1 Xuhua Wu,1 Qingquan Xia,2 Jie Chen,1 Xiaofan Yin2 1Department of Orthopedics, The First Affiliated Hospital of Soochow University, Soochow, 215006, People’s Republic of China; 2Department of Orthopedics, Minhang Hospital, Fudan University, Shanghai, 201199, People’s Republic of ChinaCorrespondence: Weimin JiangDepartment of Orthopedics, The First Affiliated Hospital of Soochow University, No. 899, Pinghai Road, Soochow, 215006, People’s Republic of ChinaTel +86-512-65223637Email [email protected]: Osteonecrosis of the femoral head (ONFH) seriously affects the quality of life and labor ability of patients. It is urgent and vital to find the methods for necrosis clinical treatment.Objective: This study aims to study the potential protective effects of Alendronate in the early stage of femur head necrosis.Methods: Ten clinal ONFH tissue samples were employed. H&E staining was employed for the observation of the pathological characteristics of ONFH. The rat model (n=12) was established by the treatment of liquid nitrogen and then treated with Alendronate. The protein expression of BMP2, EIF2AK3, EIF2A and ATF4 were detected via Western blotting and IHC.Results: Fibrin and necrotizing granulation tissue were observed in ONFH tissues with lymphocytes and plasma cells infiltrating in the necrotic area, exhibiting the inflammatory muscle with abnormal shape and color. In the Model group, the BMP2 and ATF4 were mainly distributed in the cell boundaries. The relative protein expression of BMP2, EIF2AK3, EIF2A, ATF4 was decreased in the Model group, compared to the NC group, which was partially recovered by the Alendronate application.Conclusion: Alendronate application partially reversed the suppression of expression of BMP2, EIF2AK3, EIF2A, ATF4 caused by liquid nitrogen. Alendronate could be a promising strategy of curing ONFH via targeting BMP2/EIF2AK3/EIF2A/ATF4 pathway.Keywords: femoral head necrosis, alendronate, BMP2, ATF4

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