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阿仑膦酸钠减轻液氮处理大鼠股骨头坏死并上调 BMP2/EIF2AK3/EIF2A/ATF4 通路。

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

机构信息

Department of Orthopedics, The First Affiliated Hospital of Soochow University, Soochow, 215006, People's Republic of China.

Department of Orthopedics, Minhang Hospital, Fudan University, Shanghai, 201199, People's Republic of China.

出版信息

Drug Des Devel Ther. 2021 Apr 23;15:1717-1724. doi: 10.2147/DDDT.S286610. eCollection 2021.

DOI:10.2147/DDDT.S286610
PMID:33935494
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8079257/
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.

摘要

背景

股骨头坏死（ONFH）严重影响患者的生活质量和劳动能力。寻找坏死的临床治疗方法迫在眉睫。

目的

本研究旨在探讨阿仑膦酸钠对早期股骨头坏死的潜在保护作用。

方法

临床收集 10 例 ONFH 组织标本，行 H&E 染色观察 ONFH 的病理特征，液氮处理建立大鼠模型，再给予阿仑膦酸钠处理。采用 Western blot 和 IHC 检测 BMP2、EIF2AK3、EIF2A 和 ATF4 的蛋白表达。

结果

ONFH 组织中可见纤维蛋白和坏死肉芽组织，坏死区有淋巴细胞和浆细胞浸润，表现为形态和颜色异常的炎性肌。模型组 BMP2 和 ATF4 主要分布在细胞边界，模型组 BMP2、EIF2AK3、EIF2A、ATF4 的相对蛋白表达较 NC 组降低，阿仑膦酸钠处理部分恢复。

结论

阿仑膦酸钠应用部分逆转了液氮引起的 BMP2、EIF2AK3、EIF2A、ATF4 表达抑制。阿仑膦酸钠可能通过靶向 BMP2/EIF2AK3/EIF2A/ATF4 通路成为治疗 ONFH 的有前途的策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/332c/8079257/dd75fef86282/DDDT-15-1717-g0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/332c/8079257/eceba036d110/DDDT-15-1717-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/332c/8079257/300261172be8/DDDT-15-1717-g0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/332c/8079257/6be254bcf56a/DDDT-15-1717-g0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/332c/8079257/ebea0581e851/DDDT-15-1717-g0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/332c/8079257/dd75fef86282/DDDT-15-1717-g0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/332c/8079257/eceba036d110/DDDT-15-1717-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/332c/8079257/300261172be8/DDDT-15-1717-g0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/332c/8079257/6be254bcf56a/DDDT-15-1717-g0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/332c/8079257/ebea0581e851/DDDT-15-1717-g0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/332c/8079257/dd75fef86282/DDDT-15-1717-g0005.jpg

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