Dexamethasone promotes the endoplasmic reticulum stress response of bone marrow mesenchymal stem cells by activating the PERK‐Nrf2 signaling pathway

• Main Authors: Suoli Cheng, Xueqin Liu, Fan Gong, Xiaoling Ding, Xuebing Zhou, Cuiyun Liu, Fei Zhao, Xiaoliang Li, Jiandang Shi
• Format: Article
• Language: English
• Published: Wiley 2021-05-01
• Series: Pharmacology Research & Perspectives
• Subjects: bone marrow mesenchymal stem cells; dexamethasone; endoplasmic reticulum stress; steroid‐induced avascular necrosis of femoral head
• Online Access: https://doi.org/10.1002/prp2.791

Abstract The pathogenesis of steroid‐induced avascular necrosis of femoral head (SANFH) is complex, and there is a lack of effective early prevention method. The aim of the present study was to evaluate the effect of dexamethasone (DEX) on the biological behavior of bone marrow mesenchymal stem cells (BMSCs) and to explore the possibility of DEX in the clinical treatment of SANFH. The effect of DEX on the proliferation of BMSCs was evaluated by Counting Kit‐8 assay, western blot assay, and enzyme‐linked immunosorbent assay. Flow cytometry and western blot assay were performed to detect the effect of DEX on the apoptosis of BMSCs. Quantitative real‐time PCR and western blot assay were performed to detect the effect of DEX on the expression of endoplasmic reticulum stress (ERS)‐related genes. Immunoblotting analysis was conducted for detecting the nuclear‐cytoplasmic distribution of Nrf2. DEX could significantly inhibit the proliferation of BMSCs and promote apoptosis of BMSCs. DEX could increase the expression of PERK, ATF6, and IRE1a, and induce nuclear translocation of Nrf2. The addition of ML385 could reverse the effect of DEX on BMSCs. DEX could activate the PERK‐Nrf2 pathway to promote ERS and finally affect the cell proliferation and apoptosis of BMSCs.