Uncovering pathways regulating chondrogenic differentiation of CHH fibroblasts
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...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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KeAi Communications Co., Ltd.
2021-12-01
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| Series: | Non-coding RNA Research |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2468054021000470 |
| _version_ | 1797203943196983296 |
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| author | Alzbeta Chabronova Guus G.H. van den Akker Mandy M.F. Meekels-Steinbusch Franziska Friedrich Andy Cremers Don A.M. Surtel Mandy J. Peffers Lodewijk W. van Rhijn Ekkehart Lausch Bernhard Zabel Marjolein M.J. Caron Tim J.M. Welting |
| author_facet | Alzbeta Chabronova Guus G.H. van den Akker Mandy M.F. Meekels-Steinbusch Franziska Friedrich Andy Cremers Don A.M. Surtel Mandy J. Peffers Lodewijk W. van Rhijn Ekkehart Lausch Bernhard Zabel Marjolein M.J. Caron Tim J.M. Welting |
| author_sort | Alzbeta Chabronova |
| collection | DOAJ |
| description | 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 in vitro 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 RMRP during chondrogenic differentiation and the relevance and roles of non-coding RNAs in genetic diseases in general. |
| first_indexed | 2024-04-24T08:27:21Z |
| format | Article |
| id | doaj.art-d37c8f7d561c4191a6c92acb6d382bcf |
| institution | Directory Open Access Journal |
| issn | 2468-0540 |
| language | English |
| last_indexed | 2024-04-24T08:27:21Z |
| publishDate | 2021-12-01 |
| publisher | KeAi Communications Co., Ltd. |
| record_format | Article |
| series | Non-coding RNA Research |
| spelling | doaj.art-d37c8f7d561c4191a6c92acb6d382bcf2024-04-16T21:45:56ZengKeAi Communications Co., Ltd.Non-coding RNA Research2468-05402021-12-0164211224Uncovering pathways regulating chondrogenic differentiation of CHH fibroblastsAlzbeta Chabronova0Guus G.H. van den Akker1Mandy M.F. Meekels-Steinbusch2Franziska Friedrich3Andy Cremers4Don A.M. Surtel5Mandy J. Peffers6Lodewijk W. van Rhijn7Ekkehart Lausch8Bernhard Zabel9Marjolein M.J. Caron10Tim J.M. Welting11Laboratory for Experimental Orthopedics, Department of Orthopedic Surgery, MUMC+, 6202, AZ, Maastricht, the NetherlandsLaboratory for Experimental Orthopedics, Department of Orthopedic Surgery, MUMC+, 6202, AZ, Maastricht, the NetherlandsLaboratory for Experimental Orthopedics, Department of Orthopedic Surgery, MUMC+, 6202, AZ, Maastricht, the NetherlandsDepartment of Pediatrics, Medical Center, University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, GermanyLaboratory for Experimental Orthopedics, Department of Orthopedic Surgery, MUMC+, 6202, AZ, Maastricht, the NetherlandsLaboratory for Experimental Orthopedics, Department of Orthopedic Surgery, MUMC+, 6202, AZ, Maastricht, the NetherlandsInstitute of Life Course and Medical Sciences, University of Liverpool, William Henry Duncan Building, 6 West Derby Street, Liverpool, L7 8TX, UKLaboratory for Experimental Orthopedics, Department of Orthopedic Surgery, MUMC+, 6202, AZ, Maastricht, the NetherlandsDepartment of Pediatrics, Medical Center, University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, GermanyMedical Faculty, Otto van Guericke University of Magdeburg, 39106, Magdeburg, GermanyLaboratory for Experimental Orthopedics, Department of Orthopedic Surgery, MUMC+, 6202, AZ, Maastricht, the NetherlandsLaboratory for Experimental Orthopedics, Department of Orthopedic Surgery, MUMC+, 6202, AZ, Maastricht, the Netherlands; Corresponding author.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 in vitro 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 RMRP during chondrogenic differentiation and the relevance and roles of non-coding RNAs in genetic diseases in general.http://www.sciencedirect.com/science/article/pii/S2468054021000470RMRPsnoRNACartilage-hair hypoplasiaTranscriptomeTransdifferentiationChondrocyte |
| spellingShingle | Alzbeta Chabronova Guus G.H. van den Akker Mandy M.F. Meekels-Steinbusch Franziska Friedrich Andy Cremers Don A.M. Surtel Mandy J. Peffers Lodewijk W. van Rhijn Ekkehart Lausch Bernhard Zabel Marjolein M.J. Caron Tim J.M. Welting Uncovering pathways regulating chondrogenic differentiation of CHH fibroblasts Non-coding RNA Research RMRP snoRNA Cartilage-hair hypoplasia Transcriptome Transdifferentiation Chondrocyte |
| title | Uncovering pathways regulating chondrogenic differentiation of CHH fibroblasts |
| title_full | Uncovering pathways regulating chondrogenic differentiation of CHH fibroblasts |
| title_fullStr | Uncovering pathways regulating chondrogenic differentiation of CHH fibroblasts |
| title_full_unstemmed | Uncovering pathways regulating chondrogenic differentiation of CHH fibroblasts |
| title_short | Uncovering pathways regulating chondrogenic differentiation of CHH fibroblasts |
| title_sort | uncovering pathways regulating chondrogenic differentiation of chh fibroblasts |
| topic | RMRP snoRNA Cartilage-hair hypoplasia Transcriptome Transdifferentiation Chondrocyte |
| url | http://www.sciencedirect.com/science/article/pii/S2468054021000470 |
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