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miR-365 Ameliorates Dexamethasone-Induced Suppression of Osteogenesis in MC3T3-E1 Cells by Targeting HDAC4.
- Source :
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International journal of molecular sciences [Int J Mol Sci] 2017 May 04; Vol. 18 (5). Date of Electronic Publication: 2017 May 04. - Publication Year :
- 2017
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Abstract
- 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.
- Subjects :
- 3' Untranslated Regions
Animals
Cell Line
Collagen Type I genetics
Collagen Type I metabolism
Core Binding Factor Alpha 1 Subunit genetics
Core Binding Factor Alpha 1 Subunit metabolism
Dexamethasone pharmacology
Histone Deacetylases metabolism
Mice
MicroRNAs metabolism
Osteoblasts cytology
Osteoblasts drug effects
Osteoblasts metabolism
Osteopontin genetics
Osteopontin metabolism
Histone Deacetylases genetics
MicroRNAs genetics
Osteogenesis
Subjects
Details
- Language :
- English
- ISSN :
- 1422-0067
- Volume :
- 18
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- International journal of molecular sciences
- Publication Type :
- Academic Journal
- Accession number :
- 28471397
- Full Text :
- https://doi.org/10.3390/ijms18050977