Chabronova, Alzbeta, van den Akker, Guus GH, Meekels-Steinbusch, Mandy MF, Friedrich, Franziska, Cremers, Andy, Surtel, Don AM, Peffers, Mandy J 
ORCID: 0000-0001-6979-0440, van Rhijn, Lodewijk W, Lausch, Ekkehart, Zabel, Bernhard et al (show 2 more authors)
(2021)
Uncovering pathways regulating chondrogenic differentiation of CHH fibroblasts.
NON-CODING RNA RESEARCH, 6 (4).
pp. 211-224.
Abstract
Mutations in the non-coding snoRNA component of mitochondrial RNA processing endoribonuclease (RMRP) are the cause of cartilage-hair hypoplasia (CHH). CHH is a rare form of metaphyseal chondrodysplasia characterized by disproportionate short stature and abnormal growth plate development. The process of chondrogenic differentiation within growth plates of long bones is vital for longitudinal bone growth. However, molecular mechanisms behind impaired skeletal development in CHH patients remain unclear. We employed a transdifferentiation model (FDC) combined with whole transcriptome analysis to investigate the chondrogenic transdifferentiation capacity of CHH fibroblasts and to examine pathway regulation in CHH cells during chondrogenic differentiation. We established that the FDC transdifferentiation model is a relevant <i>in vitro</i> model of chondrogenic differentiation, with an emphasis on the terminal differentiation phase, which is crucial for longitudinal bone growth. We demonstrated that CHH fibroblasts are capable of transdifferentiating into chondrocyte-like cells, and show a reduced commitment to terminal differentiation. We also found a number of key factors of BMP, FGF, and IGF-1 signalling axes to be significantly upregulated in CHH cells during the chondrogenic transdifferentiation. Our results support postulated conclusions that RMRP has pleiotropic functions and profoundly affects multiple aspects of cell fate and signalling. Our findings shed light on the consequences of pathological CHH mutations in snoRNA <i>RMRP</i> during chondrogenic differentiation and the relevance and roles of non-coding RNAs in genetic diseases in general.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | RMRP, snoRNA, Cartilage-hair hypoplasia, Transcriptome, Transdifferentiation, Chondrocyte |
| Divisions: | Faculty of Health and Life Sciences Faculty of Health and Life Sciences > Institute of Life Courses and Medical Sciences |
| Depositing User: | Symplectic Admin |
| Date Deposited: | 11 Jan 2022 14:30 |
| Last Modified: | 18 Jan 2023 21:16 |
| DOI: | 10.1016/j.ncrna.2021.12.003 |
| Open Access URL: | https://doi.org/10.1016/j.ncrna.2021.12.003 |
| Related URLs: | |
| URI: | https://livrepository.liverpool.ac.uk/id/eprint/3146529 |
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