MiR-455-3p activates Nrf2/ARE signaling via HDAC2 and protects osteoblasts from oxidative stress.

Abstract

BACKGROUND:

The important role of miR-455-3p in the pathogenesis of bone metabolism associated diseases is gradually emerging. This study aims to ascertain the involvement of miR-455-3p and its underlying mechanisms in osteoporosis.

METHODS:

The osteoblast cell lines MC3T3-E1 was treated with ferric ammonium citrate (FAC) to mimic a pathological environment for osteoporosis. The cytotoxic effect of iron overload was assessed by proliferation, apoptosis and oxidative stress of osteoblasts using commercial kits. Molecular biological methods, including qRT-PCR analysis, cell transfection and luciferase reporter assays were used to explain the role of miR-455-3p and its potential mechanisms in osteoblast apoptosis.

RESULTS:

FAC dramatically inhibited the proliferation of osteoblast cells MC3T3-E1 but increased the apoptosis. We also observed that FAC significantly down-regulated miR-455-3p in MC3T3-E1 cells but enhanced HDAC2 protein level. Moreover, miR-455-3p overexpression eliminated the effects of iron overload on osteoblast cell proliferation, apoptosis and oxidative stress. In addition, miR-455-3p regulated osteoblast cell proliferation, apoptosis and oxidative stress through regulating HDAC2-Nrf2/ARE signaling pathway. MiR-455-3p overexpression alleviated the oxidative stress injury in osteoporosis mice.

CONCLUSION:

Our results demonstrated that miR-455-3p activated Nrf2/ARE signal pathway through suppressing Keap1 via negative regulating HDAC2 protein level, thereby suppressing oxidative stress and promoting osteoblasts growth.

• Authors: Shijun Zhang, Wenliang Wu, Guangjun Jiao, Ci Li, Haichun Liu
• Journal: International journal of biological macromolecules (Int J Biol Macromol) Vol. 107 Issue Pt B Pg. 2094-2101 (Feb 2018) ISSN: 1879-0003 [Electronic] Netherlands
• PMID: 29042277 (Publication Type: Journal Article)
• Copyright: Copyright © 2017 Elsevier B.V. All rights reserved.

Chemical References

• Keap1 protein, mouse
• Kelch-Like ECH-Associated Protein 1
• MIRN455 microRNA, mouse
• MicroRNAs
• NF-E2-Related Factor 2
• Iron
• Hdac2 protein, mouse
• Histone Deacetylase 2

Topics

• Animals
• Antioxidant Response Elements (genetics)
• Apoptosis
• Base Sequence
• Cell Differentiation
• Cell Line
• Cytoprotection
• Histone Deacetylase 2 (metabolism)
• Iron (metabolism)
• Kelch-Like ECH-Associated Protein 1
• Mice
• MicroRNAs (genetics, metabolism)
• NF-E2-Related Factor 2 (metabolism)
• Osteoblasts (metabolism, pathology)
• Osteoporosis (pathology)
• Oxidative Stress
• Signal Transduction