Steinbusch, Mandy M. F.;
Caron, Marjolein M. J.;
Surtel, Don A. M.;
Friedrich, Franziska;
Lausch, Ekkehart;
Pruijn, Ger J. M.;
Verhesen, Wouter;
Schroen, Blanche L. M.;
van Rhijn, Lodewijk W.;
Zabel, Bernhard;
Welting, Tim J. M.
Expression of RMRP RNA is regulated in chondrocyte hypertrophy and determines chondrogenic differentiation
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Media type:
E-Article
Title:
Expression of RMRP RNA is regulated in chondrocyte hypertrophy and determines chondrogenic differentiation
Contributor:
Steinbusch, Mandy M. F.;
Caron, Marjolein M. J.;
Surtel, Don A. M.;
Friedrich, Franziska;
Lausch, Ekkehart;
Pruijn, Ger J. M.;
Verhesen, Wouter;
Schroen, Blanche L. M.;
van Rhijn, Lodewijk W.;
Zabel, Bernhard;
Welting, Tim J. M.
Published:
Springer Science and Business Media LLC, 2017
Published in:
Scientific Reports, 7 (2017) 1
Language:
English
DOI:
10.1038/s41598-017-06809-5
ISSN:
2045-2322
Origination:
Footnote:
Description:
AbstractMutations in theRMRP-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 inRMRPRNA lead to skeletal dysplasia. Since chondrogenic differentiation of the growth plate is required for development of long bones, we hypothesized thatRMRPRNA plays a pivotal role in chondrogenic differentiation. Expression ofRmrpRNA and RNase MRP protein subunits was detected in the murine growth plate and during the course of chondrogenic differentiation of ATDC5 cultures, whereRmrpRNA expression was found to be correlated with chondrocyte hypertrophy. Genetic interference withRmrpRNA 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 thatRmrpRNA 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 thatRMRPRNA expression is regulated during different stages of chondrogenic differentiation and indicate thatRMRPRNA may play a pivotal role in chondrocyte hypertrophy, with potential consequences for CHH pathobiology.