miR-365 Ameliorates Dexamethasone-Induced Suppression of Osteogenesis in MC3T3-E1 Cells by Targeting HDAC4
AbstractGlucocorticoid administration is the leading cause of secondary osteoporosis. In this study, we tested the hypotheses that histone deacetylase 4 (HDAC4) is associated with glucocorticoid-induced bone loss and that HDAC4 dependent bone loss can be ameliorated by miRNA-365. Our previous studies showed that miR-365 mediates mechanical stimulation of chondrocyte proliferation and differentiation by targeting HDAC4. However, it is not clear whether miR-365 has an effect on glucocorticoid-induced osteoporosis. We have shown that, in MC3T3-E1 osteoblasts, dexamethasone (DEX) treatment decreased the expression of miR-365, which is accompanied by the decrease of cell viability in a dose-dependent manner. Transfection of miR-365 ameliorated DEX-induced inhibition of MC3T3-E1 cell viability and alkaline phosphatase activity, and attenuated the suppressive effect of DEX on runt-related transcription factor 2 (Runx2), osteopontin (OPN), and collagen 1a1 (Col1a1) osteogenic gene expression. In addition, miR-365 decreased the expression of HDAC4 mRNA and protein by direct targeting the 3′-untranslated regions (3′-UTR) of HDAC4 mRNA in osteoblasts. MiR-365 increased Runx2 expression and such stimulatory effect could be reversed by HDAC4 over-expression in osteoblasts. Collectively, our findings indicate that miR-365 ameliorates DEX-induced suppression of cell viability and osteogenesis by regulating the expression of HDAC4 in osteoblasts, suggesting miR-365 might be a novel therapeutic agent for treatment of glucocorticoid-induced osteoporosis. View Full-Text
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Xu, D.; Gao, Y.; Hu, N.; Wu, L.; Chen, Q. miR-365 Ameliorates Dexamethasone-Induced Suppression of Osteogenesis in MC3T3-E1 Cells by Targeting HDAC4. Int. J. Mol. Sci. 2017, 18, 977.
Xu D, Gao Y, Hu N, Wu L, Chen Q. miR-365 Ameliorates Dexamethasone-Induced Suppression of Osteogenesis in MC3T3-E1 Cells by Targeting HDAC4. International Journal of Molecular Sciences. 2017; 18(5):977.Chicago/Turabian Style
Xu, Daohua; Gao, Yun; Hu, Nan; Wu, Longhuo; Chen, Qian. 2017. "miR-365 Ameliorates Dexamethasone-Induced Suppression of Osteogenesis in MC3T3-E1 Cells by Targeting HDAC4." Int. J. Mol. Sci. 18, no. 5: 977.
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