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BMP7 increases protein synthesis in SW1353 cells and determines rRNA levels in a NKX3-2-dependent manner
BMP7 is a morphogen capable of counteracting the OA chondrocyte hypertrophic phenotype via NKX3-2. NKX3-2 represses expression of RUNX2, an important transcription factor for chondrocyte hypertrophy. Since RUNX2 has previously been described as an inhibitor for 47S pre-rRNA transcription, we hypothe...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8827423/ https://www.ncbi.nlm.nih.gov/pubmed/35139106 http://dx.doi.org/10.1371/journal.pone.0263430 |
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author | Ripmeester, Ellen G. J. Welting, Tim J. M. van den Akker, Guus G. H. Surtel, Don A. M. Steijns, Jessica S. J. Cremers, Andy van Rhijn, Lodewijk W. Caron, Marjolein M. J. |
author_facet | Ripmeester, Ellen G. J. Welting, Tim J. M. van den Akker, Guus G. H. Surtel, Don A. M. Steijns, Jessica S. J. Cremers, Andy van Rhijn, Lodewijk W. Caron, Marjolein M. J. |
author_sort | Ripmeester, Ellen G. J. |
collection | PubMed |
description | BMP7 is a morphogen capable of counteracting the OA chondrocyte hypertrophic phenotype via NKX3-2. NKX3-2 represses expression of RUNX2, an important transcription factor for chondrocyte hypertrophy. Since RUNX2 has previously been described as an inhibitor for 47S pre-rRNA transcription, we hypothesized that BMP7 positively influences 47S pre-rRNA transcription through NKX3-2, resulting in increased protein translational capacity. Therefor SW1353 cells and human primary chondrocytes were exposed to BMP7 and rRNA (18S, 5.8S, 28S) expression was determined by RT-qPCR. NKX3-2 knockdown was achieved via transfection of a NKX3-2-specific siRNA duplex. Translational capacity was assessed by the SUNsET assay, and 47S pre-rRNA transcription was determined by transfection of a 47S gene promoter-reporter plasmid. BMP7 treatment increased protein translational capacity. This was associated by increased 18S and 5.8S rRNA and NKX3-2 mRNA expression, as well as increased 47S gene promotor activity. Knockdown of NKX3-2 led to increased expression of RUNX2, accompanied by decreased 47S gene promotor activity and rRNA expression, an effect BMP7 was unable to restore. Our data demonstrate that BMP7 positively influences protein translation capacity of SW1353 cells and chondrocytes. This is likely caused by an NKX3-2-dependent activation of 47S gene promotor activity. This finding connects morphogen-mediated changes in cellular differentiation to an aspect of ribosome biogenesis via key transcription factors central to determining the chondrocyte phenotype. |
format | Online Article Text |
id | pubmed-8827423 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-88274232022-02-10 BMP7 increases protein synthesis in SW1353 cells and determines rRNA levels in a NKX3-2-dependent manner Ripmeester, Ellen G. J. Welting, Tim J. M. van den Akker, Guus G. H. Surtel, Don A. M. Steijns, Jessica S. J. Cremers, Andy van Rhijn, Lodewijk W. Caron, Marjolein M. J. PLoS One Research Article BMP7 is a morphogen capable of counteracting the OA chondrocyte hypertrophic phenotype via NKX3-2. NKX3-2 represses expression of RUNX2, an important transcription factor for chondrocyte hypertrophy. Since RUNX2 has previously been described as an inhibitor for 47S pre-rRNA transcription, we hypothesized that BMP7 positively influences 47S pre-rRNA transcription through NKX3-2, resulting in increased protein translational capacity. Therefor SW1353 cells and human primary chondrocytes were exposed to BMP7 and rRNA (18S, 5.8S, 28S) expression was determined by RT-qPCR. NKX3-2 knockdown was achieved via transfection of a NKX3-2-specific siRNA duplex. Translational capacity was assessed by the SUNsET assay, and 47S pre-rRNA transcription was determined by transfection of a 47S gene promoter-reporter plasmid. BMP7 treatment increased protein translational capacity. This was associated by increased 18S and 5.8S rRNA and NKX3-2 mRNA expression, as well as increased 47S gene promotor activity. Knockdown of NKX3-2 led to increased expression of RUNX2, accompanied by decreased 47S gene promotor activity and rRNA expression, an effect BMP7 was unable to restore. Our data demonstrate that BMP7 positively influences protein translation capacity of SW1353 cells and chondrocytes. This is likely caused by an NKX3-2-dependent activation of 47S gene promotor activity. This finding connects morphogen-mediated changes in cellular differentiation to an aspect of ribosome biogenesis via key transcription factors central to determining the chondrocyte phenotype. Public Library of Science 2022-02-09 /pmc/articles/PMC8827423/ /pubmed/35139106 http://dx.doi.org/10.1371/journal.pone.0263430 Text en © 2022 Ripmeester et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Ripmeester, Ellen G. J. Welting, Tim J. M. van den Akker, Guus G. H. Surtel, Don A. M. Steijns, Jessica S. J. Cremers, Andy van Rhijn, Lodewijk W. Caron, Marjolein M. J. BMP7 increases protein synthesis in SW1353 cells and determines rRNA levels in a NKX3-2-dependent manner |
title | BMP7 increases protein synthesis in SW1353 cells and determines rRNA levels in a NKX3-2-dependent manner |
title_full | BMP7 increases protein synthesis in SW1353 cells and determines rRNA levels in a NKX3-2-dependent manner |
title_fullStr | BMP7 increases protein synthesis in SW1353 cells and determines rRNA levels in a NKX3-2-dependent manner |
title_full_unstemmed | BMP7 increases protein synthesis in SW1353 cells and determines rRNA levels in a NKX3-2-dependent manner |
title_short | BMP7 increases protein synthesis in SW1353 cells and determines rRNA levels in a NKX3-2-dependent manner |
title_sort | bmp7 increases protein synthesis in sw1353 cells and determines rrna levels in a nkx3-2-dependent manner |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8827423/ https://www.ncbi.nlm.nih.gov/pubmed/35139106 http://dx.doi.org/10.1371/journal.pone.0263430 |
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