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.

• Authors: Ke Rong, Xiaoliu Li, Weimin Jiang, Xuhua Wu, Qingquan Xia, Jie Chen, Xiaofan Yin
• Journal: Drug design, development and therapy (Drug Des Devel Ther) Vol. 15 Pg. 1717-1724 ( 2021) ISSN: 1177-8881 [Electronic] New Zealand
• PMID: 33935494 (Publication Type: Journal Article)
• Copyright: © 2021 Rong et al.

Chemical References

• ATF4 protein, human
• BMP2 protein, human
• Bone Morphogenetic Protein 2
• Activating Transcription Factor 4
• EIF2AK3 protein, human
• eIF-2 Kinase
• Nitrogen
• Alendronate

Topics

• Activating Transcription Factor 4 (antagonists & inhibitors, genetics, metabolism)
• Alendronate (pharmacology)
• Animals
• Bone Morphogenetic Protein 2 (antagonists & inhibitors, genetics, metabolism)
• Female
• Femur Head Necrosis (drug therapy, metabolism, pathology)
• Humans
• Male
• Middle Aged
• Nitrogen (pharmacology)
• Osteonecrosis (drug therapy, metabolism, pathology)
• Rats
• Rats, Sprague-Dawley
• Up-Regulation (drug effects)
• eIF-2 Kinase (antagonists & inhibitors, genetics, metabolism)