Low-dose Dexamethasone Promotes Osteoblast Viability by Activating Autophagy Via the SGK1/FOXO3a Signaling Pathway

Overview

Journal Cell Biol Int

Specialty Cell Biology

Date 2022 Dec 1

PMID 36453461

Authors

Xiang-Hua Yu

Xiao-Ming Xu

Sheng-Xiang Zhang

Affiliations

Soon will be listed here.

Abstract

Autophagy contributes to bone homeostasis and development under physiological conditions. Although previous studies have demonstrated the induction of the autophagy machinery by endogenous glucocorticoids (GCs), the precise mechanisms involved have not yet been clarified. The current study aimed to explore the effect of a low dose of GC (10 M dexamethasone, Dex) on autophagy in mouse embryonic osteoblastic precursor cells (MC3T3-E1 cells) and the potential mechanisms. The results showed that 10 M Dex induced significant time-dependent increases in the expression and activation of serum- and glucocorticoid-induced kinase-1 (SGK1) in MC3T3-E1 cells and that these effects were accompanied by increased cell viability and decreased apoptosis. The autophagy inhibitor 3-MA significantly inhibited Dex-mediated promotion of viability. Moreover, Dex increased LC3II and Beclin-1 levels and decreased SQSTM/p62 levels in a time-dependent manner, and these effects were attenuated by pretreatment with 3-MA. Transfection of Dex-treated MC3T3-E1 cells with shRNA-SGK1 resulted in a significant reduction in cell viability and an increase in apoptosis. 3-MA further exacerbated these effects of SGK1 inhibition. Knocking down SGK1 before Dex exposure significantly reduced the phosphorylated forkhead box O3a (p-FOXO3a)/FOXO3 ratio, suppressed LC3II and Beclin-1 levels, and increased SQSTM/p62 levels in MC3T3-E1 cells, and these effects were amplified by 3-MA. In conclusion, the results revealed that low-dose GC treatment increased osteoblast viability by activating autophagy via the SGK1/FOXO3a pathway.

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Low-dose dexamethasone promotes osteoblast viability by activating autophagy via the SGK1/FOXO3a signaling pathway.

Yu X, Xu X, Zhang S Cell Biol Int. 2022; 47(3):669-678.

PMID: 36453461 PMC: 10108317. DOI: 10.1002/cbin.11971.

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