Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: 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.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2022
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
_version_ 1784647624741093376
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
work_keys_str_mv AT ripmeesterellengj bmp7increasesproteinsynthesisinsw1353cellsanddeterminesrrnalevelsinankx32dependentmanner
AT weltingtimjm bmp7increasesproteinsynthesisinsw1353cellsanddeterminesrrnalevelsinankx32dependentmanner
AT vandenakkerguusgh bmp7increasesproteinsynthesisinsw1353cellsanddeterminesrrnalevelsinankx32dependentmanner
AT surteldonam bmp7increasesproteinsynthesisinsw1353cellsanddeterminesrrnalevelsinankx32dependentmanner
AT steijnsjessicasj bmp7increasesproteinsynthesisinsw1353cellsanddeterminesrrnalevelsinankx32dependentmanner
AT cremersandy bmp7increasesproteinsynthesisinsw1353cellsanddeterminesrrnalevelsinankx32dependentmanner
AT vanrhijnlodewijkw bmp7increasesproteinsynthesisinsw1353cellsanddeterminesrrnalevelsinankx32dependentmanner
AT caronmarjoleinmj bmp7increasesproteinsynthesisinsw1353cellsanddeterminesrrnalevelsinankx32dependentmanner