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Int. J. Mol. Sci. 2017, 18(5), 977;

miR-365 Ameliorates Dexamethasone-Induced Suppression of Osteogenesis in MC3T3-E1 Cells by Targeting HDAC4

Department of Pharmacology, Guangdong Medical University, Dongguan 523808, China
Department of Orthopaedics, Warren Alpert Medical School of Brown University/Rhode Island Hospital, Providence, RI 02903, USA
Department of Rheumatology, the First Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710061, China
College of Pharmacy, Gannan Medical University, Ganzhou 341000, China
Bone and Joint Research Center, the First Affiliated Hospital and Frontier Institute of Science and Technology, Xi’an Jiaotong University, Xi’an 710061, China
These authors contributed equally to this work.
Author to whom correspondence should be addressed.
Academic Editor: Martin Pichler
Received: 4 April 2017 / Revised: 27 April 2017 / Accepted: 28 April 2017 / Published: 4 May 2017
(This article belongs to the Collection Regulation by Non-Coding RNAs)
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Glucocorticoid 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
Keywords: miR-365; glucocorticoid; osteoporosis; histone deacetylase 4 miR-365; glucocorticoid; osteoporosis; histone deacetylase 4

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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.

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