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  2. Silencing FOXO1 attenuates dexamethasone-induced apoptosis in osteoblastic MC3T3-E1 cells

Silencing FOXO1 attenuates dexamethasone-induced apoptosis in osteoblastic MC3T3-E1 cells

  • Biochem Biophys Res Commun. 2019 Jun 11;513(4):1019-1026. doi: 10.1016/j.bbrc.2019.04.112.
Lu Xing 1 Xiaoqi Zhang 1 Hao Feng 1 Shanshan Liu 1 Dongfang Li 1 Tomoka Hasegawa 2 Jie Guo 1 Minqi Li 3
Affiliations

Affiliations

  • 1 Shandong Provincial Key Laboratory of Oral Tissue Regeneration, Department of Bone Metabolism, School of Stomatology Shandong University, Jinan, 250012, China.
  • 2 Department of Developmental Biology of Hard Tissue, Graduate School of Dental Medicine, Hokkaido University, Sapporo, 060-8586, Japan.
  • 3 Shandong Provincial Key Laboratory of Oral Tissue Regeneration, Department of Bone Metabolism, School of Stomatology Shandong University, Jinan, 250012, China. Electronic address: liminqi@sdu.edu.cn.
Abstract

Dexamethasone (DEX), a widely used glucocorticoid with strong anti-inflammatory and immunosuppressive activities, has been reported to induce Apoptosis in osteoblasts, but the underlying mechanisms are still not comprehensively investigated. FOXO1 plays an important role in the regulation of cell proliferation and Apoptosis. Our study aims to explore the role of FOXO1 in DEX-induced Apoptosis of osteoblastic MC3T3-E1 cells through bioinformatics and experiments. We first employed bioinformatics to identify DEX-related genes and revealed their functions by GO enrichment analysis including FOXO1 associated biological processes. Expression level of FOXO1 was validated by GEO data. Then, experiments were performed to verify the hypothesis. CCK8 was used to detect cell viability and Apoptosis was detected by flow cytometry. SiRNA was used to silence FOXO1 and western-blot was employed to detect protein expression. Results demonstrated DEX-related genes involved in cell proliferation, Apoptosis and angiogenesis and FOXO1 was a regulator of Apoptosis. DEX could up-regulate FOXO1 expression, inhibit cell viability, promote Apoptosis. SiRNA-FOXO1 could attenuate DEX-induced Apoptosis in MC3T3-E1. These findings suggested DEX could affect some vital biological processes of MC3T3-E1 and FOXO1 played an essential role in DEX-induced Apoptosis in MC3T3-E1.

Keywords

Apoptosis; Dexamethasone; FOXO1; Osteoblasts.

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