microRNA-7 inhibition protects human osteoblasts from dexamethasone via activation of epidermal growth factor receptor signaling

被引:22
作者
Fan, Jian-bo [1 ,2 ]
Liu, Wei [2 ]
Zhu, Xin-hui [2 ]
Cui, Sheng-yu [2 ]
Cui, Zhi-ming [2 ]
Zhao, Jian-ning [1 ]
机构
[1] Nanjing Med Univ, Jinling Clin Med Coll, Jinling Hosp, Dept Orthoped, Nanjing 210002, Jiangsu, Peoples R China
[2] Nantong Univ, Affiliated Hosp 2, Dept Orthoped, Nantong 226001, Jiangsu, Peoples R China
基金
中国国家自然科学基金;
关键词
Osteoblasts; Dexamethasone; microRNA-7; EGFR; NONCODING RNA; CELLS; EGFR; DIFFERENTIATION; OSTEOGENESIS; SUPPRESSION; MECHANISMS; EXPRESSION; APOPTOSIS; AKT;
D O I
10.1007/s11010-019-03575-y
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Sustained dexamethasone (Dex) treatment could induce secondary osteoporosis, osteonecrosis, or even bone fractures. Dex can induce potent cytotoxicity in cultured human osteoblasts. The aim of this study was to test the potential role of microRNA-7 (miR-7), which targets the epidermal growth factor receptor (EGFR), in Dex-treated human osteoblasts. In OB-6, hFOB1.19, and primary human osteoblasts, miR-7 depletion by a lentiviral antagomiR-7 construct (LV-antagomiR-7) increased EGFR expression and downstream Akt activation, protecting cells from Dex-induced viability reduction, cell death, and apoptosis. In contrast, forced overexpression of miR-7 by a lentiviral miR-7 construct (LV-miR-7) inhibited EGFR expression and Akt activation, potentiating Dex-induced cytotoxicity in OB-6, hFOB1.19, and primary human osteoblasts. EGFR is the primary target of miR-7 in human osteoblasts. Luciferase activity of the EGFR 3-untranslated region was enhanced by LV-antagomiR-7, but decreased by LV-miR-7 in OB-6 cells. Further, LV-antagomiR-7-induced osteoblast cytoprotection against Dex was abolished by the EGFR inhibitors AG1478 and PD153035. Moreover, neither LV-antagomiR-7 nor LV-miR-7 was functional in EGFR-KO OB-6 cells. We also show that miR-7 is upregulated in the necrotic femoral head tissues of Dex-administered patients, correlating with EGFR downregulation. Together, we conclude that miR-7 inhibition protects human osteoblasts from Dex via activation of EGFR signaling.
引用
收藏
页码:113 / 121
页数:9
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