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eIF2α signaling regulates ischemic osteonecrosis through endoplasmic reticulum stress
Daquan Liu1,2,3, Yunlong Zhang1,4, Xinle Li1,3,5
1Department of Anatomy and Histology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, 300070, China.
Scientific Reports
|July 13, 2017
Summary
Endoplasmic reticulum (ER) stress contributes to osteonecrosis of the femoral head (ONFH). Salubrinal treatment improved ONFH symptoms by promoting bone healing and blood vessel growth.
Area of Science:
- Orthopedics
- Cell Biology
- Biochemistry
Background:
- Osteonecrosis of the femoral head (ONFH) is often linked to ischemia/hypoxia, leading to cellular endoplasmic reticulum (ER) stress.
- ER stress is a significant cellular response implicated in the pathogenesis of ONFH.
Purpose of the Study:
- To investigate the role of ER stress in a surgery-induced ONFH animal model.
- To evaluate the therapeutic potential of salubrinal, an ER stress inhibitor, in treating ONFH.
Main Methods:
- A surgery-induced animal model of ONFH was utilized.
- Salubrinal was administered to assess its effects on ER stress and ONFH pathology.
- Key markers of bone metabolism, angiogenesis, and ER stress were analyzed.
Main Results:
- ER stress was confirmed to be associated with ONFH development.
- Salubrinal treatment significantly ameliorated ONFH symptoms, including osteonecrosis, bone loss, and reduced vascular perfusion.
- Salubrinal enhanced osteoblast development and stimulated angiogenesis by modulating ATF4, VEGF, and other related factors.
Conclusions:
- ER stress is a critical pathological factor in surgery-induced ONFH.
- Salubrinal demonstrates therapeutic efficacy in improving ONFH by suppressing ER stress.
- Salubrinal promotes bone healing and angiogenesis, offering a potential treatment strategy for ONFH.
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