Expression of RMRP RNA is regulated in chondrocyte hypertrophy and determines chondrogenic differentiation

Abstract Mutations in the RMRP-gene, encoding the lncRNA component of the RNase MRP complex, are the origin of cartilage-hair hypoplasia. Cartilage-hair hypoplasia is associated with severe dwarfism caused by impaired skeletal development. However, it is not clear why mutations in RMRP RNA lead to s...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Mandy M. F. Steinbusch, Marjolein M. J. Caron, Don A. M. Surtel, Franziska Friedrich, Ekkehart Lausch, Ger J. M. Pruijn, Wouter Verhesen, Blanche L. M. Schroen, Lodewijk W. van Rhijn, Bernhard Zabel, Tim J. M. Welting
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/fe524fe2574a400f80a3473252df828a
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:fe524fe2574a400f80a3473252df828a
record_format	dspace
spelling	oai:doaj.org-article:fe524fe2574a400f80a3473252df828a2021-12-02T16:07:56ZExpression of RMRP RNA is regulated in chondrocyte hypertrophy and determines chondrogenic differentiation10.1038/s41598-017-06809-52045-2322https://doaj.org/article/fe524fe2574a400f80a3473252df828a2017-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-06809-5https://doaj.org/toc/2045-2322Abstract Mutations in the RMRP-gene, encoding the lncRNA component of the RNase MRP complex, are the origin of cartilage-hair hypoplasia. Cartilage-hair hypoplasia is associated with severe dwarfism caused by impaired skeletal development. However, it is not clear why mutations in RMRP RNA lead to skeletal dysplasia. Since chondrogenic differentiation of the growth plate is required for development of long bones, we hypothesized that RMRP RNA plays a pivotal role in chondrogenic differentiation. Expression of Rmrp RNA and RNase MRP protein subunits was detected in the murine growth plate and during the course of chondrogenic differentiation of ATDC5 cultures, where Rmrp RNA expression was found to be correlated with chondrocyte hypertrophy. Genetic interference with Rmrp RNA expression in ATDC5 cultures caused a deregulation of chondrogenic differentiation, with a prominent impact on hypertrophy and changes in pre-rRNA processing and rRNA levels. Promoter reporter studies showed that Rmrp RNA expression responds to chondrogenic morphogens. Chondrogenic trans-differentiation of cartilage-hair hypoplasia fibroblasts was impaired with a pronounced impact on hypertrophic differentiation. Together, our data show that RMRP RNA expression is regulated during different stages of chondrogenic differentiation and indicate that RMRP RNA may play a pivotal role in chondrocyte hypertrophy, with potential consequences for CHH pathobiology.Mandy M. F. SteinbuschMarjolein M. J. CaronDon A. M. SurtelFranziska FriedrichEkkehart LauschGer J. M. PruijnWouter VerhesenBlanche L. M. SchroenLodewijk W. van RhijnBernhard ZabelTim J. M. WeltingNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-15 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Mandy M. F. Steinbusch Marjolein M. J. Caron Don A. M. Surtel Franziska Friedrich Ekkehart Lausch Ger J. M. Pruijn Wouter Verhesen Blanche L. M. Schroen Lodewijk W. van Rhijn Bernhard Zabel Tim J. M. Welting Expression of RMRP RNA is regulated in chondrocyte hypertrophy and determines chondrogenic differentiation
description	Abstract Mutations in the RMRP-gene, encoding the lncRNA component of the RNase MRP complex, are the origin of cartilage-hair hypoplasia. Cartilage-hair hypoplasia is associated with severe dwarfism caused by impaired skeletal development. However, it is not clear why mutations in RMRP RNA lead to skeletal dysplasia. Since chondrogenic differentiation of the growth plate is required for development of long bones, we hypothesized that RMRP RNA plays a pivotal role in chondrogenic differentiation. Expression of Rmrp RNA and RNase MRP protein subunits was detected in the murine growth plate and during the course of chondrogenic differentiation of ATDC5 cultures, where Rmrp RNA expression was found to be correlated with chondrocyte hypertrophy. Genetic interference with Rmrp RNA expression in ATDC5 cultures caused a deregulation of chondrogenic differentiation, with a prominent impact on hypertrophy and changes in pre-rRNA processing and rRNA levels. Promoter reporter studies showed that Rmrp RNA expression responds to chondrogenic morphogens. Chondrogenic trans-differentiation of cartilage-hair hypoplasia fibroblasts was impaired with a pronounced impact on hypertrophic differentiation. Together, our data show that RMRP RNA expression is regulated during different stages of chondrogenic differentiation and indicate that RMRP RNA may play a pivotal role in chondrocyte hypertrophy, with potential consequences for CHH pathobiology.
format	article
author	Mandy M. F. Steinbusch Marjolein M. J. Caron Don A. M. Surtel Franziska Friedrich Ekkehart Lausch Ger J. M. Pruijn Wouter Verhesen Blanche L. M. Schroen Lodewijk W. van Rhijn Bernhard Zabel Tim J. M. Welting
author_facet	Mandy M. F. Steinbusch Marjolein M. J. Caron Don A. M. Surtel Franziska Friedrich Ekkehart Lausch Ger J. M. Pruijn Wouter Verhesen Blanche L. M. Schroen Lodewijk W. van Rhijn Bernhard Zabel Tim J. M. Welting
author_sort	Mandy M. F. Steinbusch
title	Expression of RMRP RNA is regulated in chondrocyte hypertrophy and determines chondrogenic differentiation
title_short	Expression of RMRP RNA is regulated in chondrocyte hypertrophy and determines chondrogenic differentiation
title_full	Expression of RMRP RNA is regulated in chondrocyte hypertrophy and determines chondrogenic differentiation
title_fullStr	Expression of RMRP RNA is regulated in chondrocyte hypertrophy and determines chondrogenic differentiation
title_full_unstemmed	Expression of RMRP RNA is regulated in chondrocyte hypertrophy and determines chondrogenic differentiation
title_sort	expression of rmrp rna is regulated in chondrocyte hypertrophy and determines chondrogenic differentiation
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/fe524fe2574a400f80a3473252df828a
work_keys_str_mv	AT mandymfsteinbusch expressionofrmrprnaisregulatedinchondrocytehypertrophyanddetermineschondrogenicdifferentiation AT marjoleinmjcaron expressionofrmrprnaisregulatedinchondrocytehypertrophyanddetermineschondrogenicdifferentiation AT donamsurtel expressionofrmrprnaisregulatedinchondrocytehypertrophyanddetermineschondrogenicdifferentiation AT franziskafriedrich expressionofrmrprnaisregulatedinchondrocytehypertrophyanddetermineschondrogenicdifferentiation AT ekkehartlausch expressionofrmrprnaisregulatedinchondrocytehypertrophyanddetermineschondrogenicdifferentiation AT gerjmpruijn expressionofrmrprnaisregulatedinchondrocytehypertrophyanddetermineschondrogenicdifferentiation AT wouterverhesen expressionofrmrprnaisregulatedinchondrocytehypertrophyanddetermineschondrogenicdifferentiation AT blanchelmschroen expressionofrmrprnaisregulatedinchondrocytehypertrophyanddetermineschondrogenicdifferentiation AT lodewijkwvanrhijn expressionofrmrprnaisregulatedinchondrocytehypertrophyanddetermineschondrogenicdifferentiation AT bernhardzabel expressionofrmrprnaisregulatedinchondrocytehypertrophyanddetermineschondrogenicdifferentiation AT timjmwelting expressionofrmrprnaisregulatedinchondrocytehypertrophyanddetermineschondrogenicdifferentiation
_version_	1718384694953771008

Expression of RMRP RNA is regulated in chondrocyte hypertrophy and determines chondrogenic differentiation

Ejemplares similares