Pro-osteoporotic miR-320a impairs osteoblast function and induces oxidative stress.
MicroRNAs (miRNAs) are important regulators of many cellular processes, including the differentiation and activity of osteoblasts, and therefore, of bone turnover. MiR-320a is overexpressed in osteoporotic bone tissue but its role in osteoblast function is unknown. In the present study, functional a...
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doaj-34039e2524754e51b84035936d564f2c2021-03-03T21:05:09ZengPublic Library of Science (PLoS)PLoS ONE1932-62032018-01-011311e020813110.1371/journal.pone.0208131Pro-osteoporotic miR-320a impairs osteoblast function and induces oxidative stress.Laura De-UgarteSusana BalcellsXavier NoguesDaniel GrinbergAdolfo Diez-PerezNatalia Garcia-GiraltMicroRNAs (miRNAs) are important regulators of many cellular processes, including the differentiation and activity of osteoblasts, and therefore, of bone turnover. MiR-320a is overexpressed in osteoporotic bone tissue but its role in osteoblast function is unknown. In the present study, functional assays were performed with the aim to elucidate the mechanism of miR-320a action in osteoblastic cells. MiR-320a was either overexpressed or inhibited in human primary osteoblasts (hOB) and gene expression changes were evaluated through microarray analysis. In addition, the effect of miR-320a on cell proliferation, viability, and oxidative stress in hOB was evaluated. Finally, matrix mineralization and alkaline phosphatase activity were assessed in order to evaluate osteoblast functionality. Microarray results showed miR-320a regulation of a number of key osteoblast genes and of genes involved in oxidative stress. Regulation of osteoblast differentiation and ossification appeared as the best significant biological processes (PANTHER P value = 3.74E-05; and P value = 3.06E-04, respectively). The other enriched pathway was that of the cellular response to cadmium and zinc ions, mostly by the overexpression of metallothioneins. In hOBs, overexpression of miR-320a increased cell proliferation and oxidative stress levels whereas mineralization capacity was reduced. In conclusion, overexpression of miR-320a increased stress oxidation levels and was associated with reduced osteoblast differentiation and functionality, which could trigger an osteoporotic phenotype.https://doi.org/10.1371/journal.pone.0208131 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Laura De-Ugarte Susana Balcells Xavier Nogues Daniel Grinberg Adolfo Diez-Perez Natalia Garcia-Giralt |
spellingShingle |
Laura De-Ugarte Susana Balcells Xavier Nogues Daniel Grinberg Adolfo Diez-Perez Natalia Garcia-Giralt Pro-osteoporotic miR-320a impairs osteoblast function and induces oxidative stress. PLoS ONE |
author_facet |
Laura De-Ugarte Susana Balcells Xavier Nogues Daniel Grinberg Adolfo Diez-Perez Natalia Garcia-Giralt |
author_sort |
Laura De-Ugarte |
title |
Pro-osteoporotic miR-320a impairs osteoblast function and induces oxidative stress. |
title_short |
Pro-osteoporotic miR-320a impairs osteoblast function and induces oxidative stress. |
title_full |
Pro-osteoporotic miR-320a impairs osteoblast function and induces oxidative stress. |
title_fullStr |
Pro-osteoporotic miR-320a impairs osteoblast function and induces oxidative stress. |
title_full_unstemmed |
Pro-osteoporotic miR-320a impairs osteoblast function and induces oxidative stress. |
title_sort |
pro-osteoporotic mir-320a impairs osteoblast function and induces oxidative stress. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS ONE |
issn |
1932-6203 |
publishDate |
2018-01-01 |
description |
MicroRNAs (miRNAs) are important regulators of many cellular processes, including the differentiation and activity of osteoblasts, and therefore, of bone turnover. MiR-320a is overexpressed in osteoporotic bone tissue but its role in osteoblast function is unknown. In the present study, functional assays were performed with the aim to elucidate the mechanism of miR-320a action in osteoblastic cells. MiR-320a was either overexpressed or inhibited in human primary osteoblasts (hOB) and gene expression changes were evaluated through microarray analysis. In addition, the effect of miR-320a on cell proliferation, viability, and oxidative stress in hOB was evaluated. Finally, matrix mineralization and alkaline phosphatase activity were assessed in order to evaluate osteoblast functionality. Microarray results showed miR-320a regulation of a number of key osteoblast genes and of genes involved in oxidative stress. Regulation of osteoblast differentiation and ossification appeared as the best significant biological processes (PANTHER P value = 3.74E-05; and P value = 3.06E-04, respectively). The other enriched pathway was that of the cellular response to cadmium and zinc ions, mostly by the overexpression of metallothioneins. In hOBs, overexpression of miR-320a increased cell proliferation and oxidative stress levels whereas mineralization capacity was reduced. In conclusion, overexpression of miR-320a increased stress oxidation levels and was associated with reduced osteoblast differentiation and functionality, which could trigger an osteoporotic phenotype. |
url |
https://doi.org/10.1371/journal.pone.0208131 |
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