Identifying fibroblast growth factor receptor 3 as a mediator of periosteal osteochondral differentiation through the construction of microRNA-based interaction networks
Article
Wells, L., Roberts, H., Luyten, F. and Roberts, S. 2023. Identifying fibroblast growth factor receptor 3 as a mediator of periosteal osteochondral differentiation through the construction of microRNA-based interaction networks. Biology. 12 (11). https://doi.org/10.3390/biology12111381
| Type | Article |
|---|---|
| Title | Identifying fibroblast growth factor receptor 3 as a mediator of periosteal osteochondral differentiation through the construction of microRNA-based interaction networks |
| Authors | Wells, L., Roberts, H., Luyten, F. and Roberts, S. |
| Abstract | Human periosteum-derived progenitor cells (hPDCs) have the ability to differentiate towards both the chondrogenic and osteogenic lineages. This coordinated and complex osteochondrogenic differentiation process permits endochondral ossification and is essential in bone development and repair. We have previously shown that humanised cultures of hPDCs enhance their osteochondrogenic potentials in vitro and in vivo; however, the underlying mechanisms are largely unknown. This study aimed to identify novel regulators of hPDC osteochondrogenic differentiation through the construction of miRNA-mRNA regulatory networks derived from hPDCs cultured in human serum or foetal bovine serum as an alternative in silico strategy to serum characterisation. Sixteen differentially expressed miRNAs (DEMis) were identified in the humanised culture. In silico analysis of the DEMis with TargetScan allowed for the identification of 1503 potential miRNA target genes. Upon comparison with a paired RNAseq dataset, a 4.5% overlap was observed (122 genes). A protein–protein interaction network created with STRING interestingly identified FGFR3 as a key network node, which was further predicted using multiple pathway analyses. Functional analysis revealed that hPDCs with the activating mutation FGFR3N540K displayed increased expressions of chondrogenic gene markers when cultured under chondrogenic conditions in vitro and displayed enhanced endochondral bone formation in vivo. A further histological analysis uncovered known downstream mediators involved in FGFR3 signalling and endochondral ossification to be upregulated in hPDC FGFR3N540K-seeded implants. This combinational approach of miRNA-mRNA-protein network analysis with in vitro and in vivo characterisation has permitted the identification of FGFR3 as a novel mediator of hPDC biology. Furthermore, this miRNA-based workflow may also allow for the identification of drug targets, which may be of relevance in instances of delayed fracture repair. |
| Keywords | microRNA; osteochondral differentiation; fracture repair; osteoarthritis |
| Sustainable Development Goals | 3 Good health and well-being |
| Middlesex University Theme | Health & Wellbeing |
| Publisher | MDPI AG |
| Journal | Biology |
| ISSN | |
| Electronic | 2079-7737 |
| Publication dates | |
| Online | 28 Oct 2023 |
| Nov 2023 | |
| Publication process dates | |
| Submitted | 24 Aug 2023 |
| Accepted | 24 Oct 2023 |
| Deposited | 24 Nov 2023 |
| Output status | Published |
| Publisher's version | License File Access Level Open |
| Copyright Statement | Copyright: © 2023 by the authors. Licensee MDPI, Basel, Switzerland. |
| Digital Object Identifier (DOI) | https://doi.org/10.3390/biology12111381 |
| PubMed ID | 37997980 |
| PubMed Central ID | 10669632 |
| Web of Science identifier | WOS:001107831300001 |
| MEDLINE:37997980 | |
| National Library of Medicine ID | 101587988 |
| Language | English |
Permalink -
https://repository.mdx.ac.uk/item/w52v0
Download files
94
total views27
total downloads3
views this month0
downloads this month
Export as
Related outputs
The efficacy of gemcitabine and docetaxel chemotherapy for the treatment of relapsed and refractory osteosarcoma: a systematic review and pre‐clinical study
Low, K., Foulkes, P., Hills, F., Roberts, H. and Stordal, B. 2024. The efficacy of gemcitabine and docetaxel chemotherapy for the treatment of relapsed and refractory osteosarcoma: a systematic review and pre‐clinical study. Cancer Medicine. 13 (18). https://doi.org/10.1002/cam4.70248A machine learning‑based image segmentation method to quantify in vitro osteoclast culture endpoints
Davies, B.K., Hibbert, A.P., Roberts, S.J., Roberts, H., Tickner, J.C., Holdsworth, G., Arnett, T.R. and Orriss, I.R. 2023. A machine learning‑based image segmentation method to quantify in vitro osteoclast culture endpoints. Calcified Tissue International and Musculoskeletal Research. 113 (4), p. 437–448.Establishment and characterization of single and triple‐agent resistant osteosarcoma cell lines
Low, K., Hills, F., Roberts, H. and Stordal, B. 2023. Establishment and characterization of single and triple‐agent resistant osteosarcoma cell lines. Advanced Biology. 7 (2). https://doi.org/10.1002/adbi.202200194Overcoming chemoresistance in osteosarcoma: the role of autophagy in cell death or survival following chemotherapy
Rosa, G., Burczynska, B., Stordal, B. and Roberts, H. 2018. Overcoming chemoresistance in osteosarcoma: the role of autophagy in cell death or survival following chemotherapy. Research Degrees Students' Summer Conference. Middlesex University, London, UK 04 Sep 2018Optimisation of a selection strategy for drug resistance osteosarcoma cell lines
Low, K., Hills, F., Roberts, H. and Stordal, B. 2018. Optimisation of a selection strategy for drug resistance osteosarcoma cell lines. Research Degrees Students' Summer Conference. Middlesex University, London, UK 04 Sep 2018Mechanisms of apoptosis and autophagy in chemoresistant ovarian cancer cells
Bennacer, A., Roberts, H. and Stordal, B. 2018. Mechanisms of apoptosis and autophagy in chemoresistant ovarian cancer cells. Research Degrees Students' Summer Conference. Middlesex University, London, UK 04 Sep 2018Overcoming chemoresistance in osteosarcoma: the role of autophagy in cell death or survival following chemotherapy
Rosa, G., Burczynska, B., Stordal, B. and Roberts, H. 2018. Overcoming chemoresistance in osteosarcoma: the role of autophagy in cell death or survival following chemotherapy. 2018 NCRI Cancer Conference. Glasgow, Scotland 04 - 06 Nov 2018Optimisation of a selection strategy for drug resistance osteosarcoma cell lines
Low, K., Hills, F., Roberts, H. and Stordal, B. 2019. Optimisation of a selection strategy for drug resistance osteosarcoma cell lines. 2019 NCRI Cancer Conference. Glasgow, UK 03 - 05 Nov 2019The role of autophagy in canine osteosarcoma chemoresistance and metastasis
Kulatheepan, Y., Baines, S., Meeson, R. and Roberts, H. 2022. The role of autophagy in canine osteosarcoma chemoresistance and metastasis. 26th Annual Technological Advances in Science, Medicine and Engineering Conference 2022. Virtual 27 - 28 Aug 2022ATR inhibition increases sensitivity of a highly aggressive osteosarcoma cell line to cisplatin treatment
Pereira, J., Roberts, S. and Roberts, H. 2022. ATR inhibition increases sensitivity of a highly aggressive osteosarcoma cell line to cisplatin treatment. Research Students' Summer Conference. Middlesex University, Lonon, UK 22 - 23 Jun 2022Migratory bodies express markers of tumour initiating cells and may represent an early stage of osteosarcoma sarcosphere initiation and metastasis
Paternina Martinez, D., Roberts, S. and Roberts, H. 2022. Migratory bodies express markers of tumour initiating cells and may represent an early stage of osteosarcoma sarcosphere initiation and metastasis. Research Students' Summer Conference. Middlesex University, Lonon, UK 22 - 23 Jun 2022CRISPR/Cas9-mediated ATG7 knockout results in enhanced osteosarcoma chemosensitivity
Pears, A. and Roberts, H. 2022. CRISPR/Cas9-mediated ATG7 knockout results in enhanced osteosarcoma chemosensitivity. Bone Research Society Annual Conference. Manchester Metropolitan University, Manchester, UK 06 - 08 Jul 2022ATR inhibition increases sensitivity of a highly aggressive osteosarcoma cell line to cisplatin treatment
Pereira, J., Roberts, S. and Roberts, H. 2022. ATR inhibition increases sensitivity of a highly aggressive osteosarcoma cell line to cisplatin treatment. Bone Research Society Annual Conference. Manchester Metropolitan University, Manchester, UK 06 - 08 Jul 2022Migratory bodies express markers of tumour initiating cells and may represent an early stage of osteosarcoma sarcosphere initiation and metastasis
Paternina Martinez, D., Roberts, S. and Roberts, H. 2022. Migratory bodies express markers of tumour initiating cells and may represent an early stage of osteosarcoma sarcosphere initiation and metastasis. Bone Research Society Annual Conference. Manchester Metropolitan University, Manchester, UK 06 - 08 Jul 2022Intentionality for inclusivity - the journey at Middlesex University
Roberts, H., Punev, I., Allardyce, D., Kyprianou, A., Appiah, S., Megeney, A., Calin, A., Gallacher, D. and Mill, R. 2022. Intentionality for inclusivity - the journey at Middlesex University. McGraw Hill.