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

Abstract

Background

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

Acknowledgments

We would like to acknowledge everyone for their helpful contributions on this paper. Ke Rong and  Xiaoliu Li are co-first authors.

Data Sharing Statement

The data are free access to available upon request from the corresponding author.

Ethics Approval and Consent to Participate

The ethic approval was obtained from the Ethic Committee of The First Affiliated Hospital of Soochow University and written informed consent was obtained from all patients.

Consent to Publish

All of the authors have consented to publish this research.

Author Contributions

All authors made a significant contribution to the work reported, whether that is in the conception, study design, execution, acquisition of data, analysis and interpretation, or in all these areas; took part in drafting, revising or critically reviewing the article; gave final approval of the version to be published; have agreed on the journal to which the article has been submitted; and agree to be accountable for all aspects of the work.

Disclosure

All authors declare no conflicts of interest.

Additional information

Funding

There is no funding to report.