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miR-135b expression downregulates Ppm1e to activate AMPK signaling and protect osteoblastic cells from dexamethasone
Activation of AMP-activated protein kinase (AMPK) could potently protect osteoblasts/osteoblastic cells from dexamethasone (Dex). We aim to induce AMPK activation via microRNA (“miRNA”) downregulation of its phosphatase Ppm1e. We discovered that microRNA-135b (“miR-135b”) targets the 3' untrans...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Impact Journals LLC
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5342578/ https://www.ncbi.nlm.nih.gov/pubmed/27661114 http://dx.doi.org/10.18632/oncotarget.12138 |
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author | Fan, Jian-Bo Ruan, Jian-Wei Liu, Wei Zhu, Lun-Qing Zhu, Xin-Hui Yi, Hong Cui, Sheng-Yu Zhao, Jian-Ning Cui, Zhi-Ming |
author_facet | Fan, Jian-Bo Ruan, Jian-Wei Liu, Wei Zhu, Lun-Qing Zhu, Xin-Hui Yi, Hong Cui, Sheng-Yu Zhao, Jian-Ning Cui, Zhi-Ming |
author_sort | Fan, Jian-Bo |
collection | PubMed |
description | Activation of AMP-activated protein kinase (AMPK) could potently protect osteoblasts/osteoblastic cells from dexamethasone (Dex). We aim to induce AMPK activation via microRNA (“miRNA”) downregulation of its phosphatase Ppm1e. We discovered that microRNA-135b (“miR-135b”) targets the 3' untranslated regions (UTRs) of Ppm1e. In human osteoblasticOB-6 cells and hFOB1.19 cells, forced-expression of miR-135b downregulated Ppm1e and activated AMPK signaling. miR-135b also protected osteoblastic cells from Dex. shRNA-induced knockdown of Ppm1e similarly activated AMPK and inhibited Dex-induced damages. Intriguingly, in the Ppm1e-silenced osteoblastic cells, miR-135b expression failed to offer further cytoprotection against Dex. Notably, AMPK knockdown (via shRNA) or dominant negative mutation abolished miR-135b-induced AMPK activation and cytoprotection against Dex. Molecularly, miR-135b, via activating AMPK, increased nicotinamide adenine dinucleotide phosphate (NADPH) activity and inhibited Dex-induced oxidative stress. At last, we found that miR-135b level was increased in human necrotic femoral head tissues, which was correlated with Ppm1e downregulation and AMPK activation. There results suggest that miR-135b expression downregulates Ppm1e to activate AMPK signaling, which protects osteoblastic cells from Dex. |
format | Online Article Text |
id | pubmed-5342578 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Impact Journals LLC |
record_format | MEDLINE/PubMed |
spelling | pubmed-53425782017-03-24 miR-135b expression downregulates Ppm1e to activate AMPK signaling and protect osteoblastic cells from dexamethasone Fan, Jian-Bo Ruan, Jian-Wei Liu, Wei Zhu, Lun-Qing Zhu, Xin-Hui Yi, Hong Cui, Sheng-Yu Zhao, Jian-Ning Cui, Zhi-Ming Oncotarget Research Paper Activation of AMP-activated protein kinase (AMPK) could potently protect osteoblasts/osteoblastic cells from dexamethasone (Dex). We aim to induce AMPK activation via microRNA (“miRNA”) downregulation of its phosphatase Ppm1e. We discovered that microRNA-135b (“miR-135b”) targets the 3' untranslated regions (UTRs) of Ppm1e. In human osteoblasticOB-6 cells and hFOB1.19 cells, forced-expression of miR-135b downregulated Ppm1e and activated AMPK signaling. miR-135b also protected osteoblastic cells from Dex. shRNA-induced knockdown of Ppm1e similarly activated AMPK and inhibited Dex-induced damages. Intriguingly, in the Ppm1e-silenced osteoblastic cells, miR-135b expression failed to offer further cytoprotection against Dex. Notably, AMPK knockdown (via shRNA) or dominant negative mutation abolished miR-135b-induced AMPK activation and cytoprotection against Dex. Molecularly, miR-135b, via activating AMPK, increased nicotinamide adenine dinucleotide phosphate (NADPH) activity and inhibited Dex-induced oxidative stress. At last, we found that miR-135b level was increased in human necrotic femoral head tissues, which was correlated with Ppm1e downregulation and AMPK activation. There results suggest that miR-135b expression downregulates Ppm1e to activate AMPK signaling, which protects osteoblastic cells from Dex. Impact Journals LLC 2016-09-20 /pmc/articles/PMC5342578/ /pubmed/27661114 http://dx.doi.org/10.18632/oncotarget.12138 Text en Copyright: © 2016 Fan et al. http://creativecommons.org/licenses/by/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Paper Fan, Jian-Bo Ruan, Jian-Wei Liu, Wei Zhu, Lun-Qing Zhu, Xin-Hui Yi, Hong Cui, Sheng-Yu Zhao, Jian-Ning Cui, Zhi-Ming miR-135b expression downregulates Ppm1e to activate AMPK signaling and protect osteoblastic cells from dexamethasone |
title | miR-135b expression downregulates Ppm1e to activate AMPK signaling and protect osteoblastic cells from dexamethasone |
title_full | miR-135b expression downregulates Ppm1e to activate AMPK signaling and protect osteoblastic cells from dexamethasone |
title_fullStr | miR-135b expression downregulates Ppm1e to activate AMPK signaling and protect osteoblastic cells from dexamethasone |
title_full_unstemmed | miR-135b expression downregulates Ppm1e to activate AMPK signaling and protect osteoblastic cells from dexamethasone |
title_short | miR-135b expression downregulates Ppm1e to activate AMPK signaling and protect osteoblastic cells from dexamethasone |
title_sort | mir-135b expression downregulates ppm1e to activate ampk signaling and protect osteoblastic cells from dexamethasone |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5342578/ https://www.ncbi.nlm.nih.gov/pubmed/27661114 http://dx.doi.org/10.18632/oncotarget.12138 |
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