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
TypeArticle
TitleIdentifying fibroblast growth factor receptor 3 as a mediator of periosteal osteochondral differentiation through the construction of microRNA-based interaction networks
AuthorsWells, 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.

KeywordsmicroRNA; osteochondral differentiation; fracture repair; osteoarthritis
Sustainable Development Goals3 Good health and well-being
Middlesex University ThemeHealth & Wellbeing
LanguageEnglish
PublisherMDPI
JournalBiology
ISSN
Electronic2079-7737
Publication dates
Print28 Oct 2023
Online28 Oct 2023
Publication process dates
Submitted24 Aug 2023
Accepted24 Oct 2023
Deposited24 Nov 2023
Output statusPublished
Publisher's version
License
Digital Object Identifier (DOI)https://doi.org/10.3390/biology12111381
PubMed ID37997980
PubMed Central ID10669632
Web of Science identifierWOS:001107831300001
MEDLINE:37997980
Permalink -

https://repository.mdx.ac.uk/item/w52v0

Download files


Publisher's version
  • 37
    total views
  • 8
    total downloads
  • 3
    views this month
  • 0
    downloads this month

Export as

Related outputs

A 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.202200194
The 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
ATR 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 2022
Migratory 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 2022
CRISPR/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 Univeristy 06 - 08 Jul 2022
ATR 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 Univeristy 06 - 08 Jul 2022
Migratory 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 Univeristy 06 - 08 Jul 2022
Intentionality 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.
Overcoming 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 2018
Optimisation 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 2018
Mechanisms 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 2018
Overcoming 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 2018
Optimisation 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 2019
Decellularised cartilage ECM culture coatings drive rapid and robust chondrogenic differentiation of human periosteal cells
Vas, W., Shah, M., Roberts, H. and Roberts, S. 2022. Decellularised cartilage ECM culture coatings drive rapid and robust chondrogenic differentiation of human periosteal cells. Bioengineering. 9 (5), pp. 1-11. https://doi.org/10.3390/bioengineering9050203
Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)
Klionsky, D., Roberts, H. and et al. 2021. Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition). Autophagy. 17 (1), pp. 1-382. https://doi.org/10.1080/15548627.2020.1797280
Mapping human serum induced gene networks as a basis for the creation of biomimetic periosteum for bone repair
Al Hosni, R., Shah, M., Cheema, U., Roberts, H., Luyten, F. and Roberts, S. 2020. Mapping human serum induced gene networks as a basis for the creation of biomimetic periosteum for bone repair. Cytotherapy. 22 (8), pp. 424-435.
The combination of curcumin and doxorubicin shows a selective cytotoxic effect on acute myeloid leukaemia cell line
Hasan, N., Roberts, H., Ghali, L. and Appiah, S. 2018. The combination of curcumin and doxorubicin shows a selective cytotoxic effect on acute myeloid leukaemia cell line. NCRI Cancer Conference (2018). Glasgow, Scotland 04 - 06 Nov 2018
MicroRNA profiles are associated with lymphocyte count after a major traumatic injury: a potential role for immunometabolism?
Jones, T., Torrance, H., Roberts, H., Brohi, K., Barnes, M., Knight, J., Hinds, C., Ackland, G. and O'Dwyer, M. 2018. MicroRNA profiles are associated with lymphocyte count after a major traumatic injury: a potential role for immunometabolism? British Journal of Anaesthesia Research Forum. Royal College of Anaesthetists, London 30 - 31 May 2018 Elsevier. pp. e23-e24 https://doi.org/10.1016/j.bja.2018.05.027
Phytochemical modulation of apoptosis and autophagy: strategies to overcome chemoresistance in leukaemic stem cells in the bone marrow microenvironment
Owen, H., Appiah, S., Hasan, N., Ghali, L., Elayat, G. and Bell, C. 2017. Phytochemical modulation of apoptosis and autophagy: strategies to overcome chemoresistance in leukaemic stem cells in the bone marrow microenvironment. in: Zeng, B. and Zhao, K. (ed.) Neurobiology of Chinese Herb Medicine Elsevier.
Biomimetic strategies for fracture repair: engineering the cell microenvironment for directed tissue formation
Vas, W., Shah, M., Al Hosni, R., Owen, H. and Roberts, S. 2017. Biomimetic strategies for fracture repair: engineering the cell microenvironment for directed tissue formation. Journal of Tissue Engineering. 8, pp. 1-14. https://doi.org/10.1177/2041731417704791
Systemic inflammatory response syndrome after major abdominal surgery predicted by early upregulation of TLR4 and TLR5
Lahiri, R., Derwa, Y., Bashir, Z., Giles, E., Torrance, H., Owen, H., O'Dwyer, M., O'Brien, A., Stagg, A., Bhattacharya, S., Foster, G. and Alazawi, W. 2016. Systemic inflammatory response syndrome after major abdominal surgery predicted by early upregulation of TLR4 and TLR5. Annals of Surgery. 263 (5), pp. 1028-1037. https://doi.org/10.1097/SLA.0000000000001248
Features of postoperative immune suppression are reversible with interferon gamma and independent of interleukin-6 pathways
Longbottom, E., Torrance, H., Owen, H., Fragkou, P., Hinds, C., Pearse, R. and O'Dwyer, M. 2016. Features of postoperative immune suppression are reversible with interferon gamma and independent of interleukin-6 pathways. Annals of Surgery. 264 (2), pp. 370-377. https://doi.org/10.1097/SLA.0000000000001484
T-helper cell polarisation following severe polytrauma
Torrance, H., Brohi, K., Warnes, G., Owen, H., Hinds, C., Pennington, D. and O'Dwyer, M. 2015. T-helper cell polarisation following severe polytrauma. ESICM LIVES 2015: 28th Annual Congress of European Society of Intensive Care Medicine. Berlin, Germany 03 - 07 Oct 2015 Springer Open. https://doi.org/10.1186/2197-425X-3-S1-A848
Post-operative immune suppression is reversible with interferon gamma and independent of IL-6 pathways
Longbottom, E., Torrance, H., Owen, H., Hinds, C., Pearse, R. and O'Dwyer, M. 2015. Post-operative immune suppression is reversible with interferon gamma and independent of IL-6 pathways. ESICM LIVES 2015: 28th Annual Congress of European Society of Intensive Care Medicine. Berlin, Germany 03 - 07 Oct 2015 Springer Open. https://doi.org/10.1186/2197-425X-3-S1-A820
The role of micrornas in the development of hospital acquired infection in polytrauma patients
Owen, H., Torrance, H., Barnes, M., Brohi, K., Knight, J., Hinds, C. and O'Dwyer, M. 2015. The role of micrornas in the development of hospital acquired infection in polytrauma patients. ESICM LIVES 2015: 28th Annual Congress of European Society of Intensive Care Medicine. Berlin, Germany 03 - 07 Oct 2015 Springer Open. https://doi.org/10.1186/2197-425X-3-S1-A35
Changes in gene expression following trauma are related to the age of transfused packed red blood cells
Torrance, H., Vivian, M., Brohi, K., Prowle, J., Pearse, R., Owen, H., Hinds, C. and O'Dwyer, M. 2015. Changes in gene expression following trauma are related to the age of transfused packed red blood cells. Journal of Trauma and Acute Care Surgery. 78 (3), pp. 535-542. https://doi.org/10.1097/TA.0000000000000534
The perioperative immune response
O'Dwyer, M., Owen, H. and Torrance, H. 2015. The perioperative immune response. Current Opinion in Critical Care. 21 (4), pp. 336-342. https://doi.org/10.1097/MCC.0000000000000213
Critical illness-induced bone loss is related to deficient autophagy and histone hypomethylation
Owen, H., Vanhees, I., Gunst, J., Van Cromphaut, S. and Van den Berghe, G. 2015. Critical illness-induced bone loss is related to deficient autophagy and histone hypomethylation. Intensive Care Medicine Experimental. 3. https://doi.org/10.1186/s40635-015-0052-3
Epigenetic regulatory pathways involving microRNAs may modulate the host immune response following major trauma
Owen, H., Torrance, H., Jones, T., Pearse, R., Hinds, C., Brohi, K. and O'Dwyer, M. 2015. Epigenetic regulatory pathways involving microRNAs may modulate the host immune response following major trauma. Journal of Trauma and Acute Care Surgery. 79 (5), pp. 766-772. https://doi.org/10.1097/TA.0000000000000850
Humanized culture of periosteal progenitors in allogeneic serum enhances osteogenic differentiation and in vivo bone formation
Roberts, S., Owen, H., Tam, W., Solie, L., Van Cromphaut, S., Van den Berghe, G. and Luyten, F. 2014. Humanized culture of periosteal progenitors in allogeneic serum enhances osteogenic differentiation and in vivo bone formation. Stem Cells Translational Medicine. 3 (2), pp. 218-28. https://doi.org/10.5966/sctm.2012-0137
Perioperative blood transfusion is associated with a gene transcription profile characteristic of immunosuppression: a prospective cohort study
Fragkou, P., Torrance, H., Pearse, R., Ackland, G., Prowle, J., Owen, H., Hinds, C. and O'Dwyer, M. 2014. Perioperative blood transfusion is associated with a gene transcription profile characteristic of immunosuppression: a prospective cohort study. Critical Care. 18 (5). https://doi.org/10.1186/s13054-014-0541-x
Enhanced immunoreceptor tyrosine-based activation motif signaling is related to pathological bone resorption during critical illness
Vanhees, I., Gunst, J., Janssens, T., Wauters, A., Van Herck, E., Van Cromphaut, S., Van den Berghe, G. and Owen, H. 2013. Enhanced immunoreceptor tyrosine-based activation motif signaling is related to pathological bone resorption during critical illness. Hormone and Metabolic Research. 45 (12), pp. 862-9. https://doi.org/10.1055/s-0033-1351290
Critical illness-related bone loss is associated with osteoclastic and angiogenic abnormalities
Owen, H., Vanhees, I., Solie, L., Roberts, S., Wauters, A., Luyten, F., Van Cromphaut, S. and Van den Berghe, G. 2012. Critical illness-related bone loss is associated with osteoclastic and angiogenic abnormalities. Journal of Bone and Mineral Research. 27 (7), pp. 1541-1552. https://doi.org/10.1002/jbmr.1612
Hypermethylation of CpG islands and shores around specific microRNAs and mirtrons is associated with the phenotype and presence of bladder cancer
Dudziec, E., Miah, S., Choudhry, H., Owen, H., Blizard, S., Glover, M., Hamdy, F. and Catto, J. 2011. Hypermethylation of CpG islands and shores around specific microRNAs and mirtrons is associated with the phenotype and presence of bladder cancer. Clinical Cancer Research. 17 (6), pp. 1287-1296. https://doi.org/10.1158/1078-0432.CCR-10-2017
Low frequency of epigenetic events in urothelial tumors in young patients
Owen, H., Giedl, J., Wild, P., Fine, S., Humphrey, P., Dehner, L., Amin, M., Epstein, J., Blaszyk, H., Hughes, D., Hartmann, A., Stoehr, R. and Catto, J. 2010. Low frequency of epigenetic events in urothelial tumors in young patients. The Journal of Urology. 184 (2), pp. 459-463. https://doi.org/10.1016/j.juro.2010.03.131
Chondrocyte p21(WAF1/CIP1) expression is increased by dexamethasone but does not contribute to dexamethasone-induced growth retardation in vivo
Owen, H., Ahmed, S. and Farquharson, C. 2009. Chondrocyte p21(WAF1/CIP1) expression is increased by dexamethasone but does not contribute to dexamethasone-induced growth retardation in vivo. Calcified Tissue International and Musculoskeletal Research. 85 (4), pp. 326-334. https://doi.org/10.1007/s00223-009-9276-0
Distinct microRNA alterations characterize high- and low-grade bladder cancer
Catto, J., Miah, S., Owen, H., Bryant, H., Myers, K., Dudziec, E., Larré, S., Milo, M., Rehman, I., Rosario, D., Di Martino, E., Knowles, M., Meuth, M., Harris, A. and Hamdy, F. 2009. Distinct microRNA alterations characterize high- and low-grade bladder cancer. Cancer Research. 69 (21), pp. 8472-8481. https://doi.org/10.1158/0008-5472.CAN-09-0744
Dexamethasone-induced expression of the glucocorticoid response gene lipocalin 2 in chondrocytes
Owen, H., Roberts, S., Ahmed, S. and Farquharson, C. 2008. Dexamethasone-induced expression of the glucocorticoid response gene lipocalin 2 in chondrocytes. American Journal of Physiology - Endocrinology and Metabolism. 294 (6), pp. E1023-E1034. https://doi.org/10.1152/ajpendo.00586.2007
Identification of a novel splice variant of the haloacid dehalogenase: PHOSPHO1
Roberts, S., Owen, H. and Farquharson, C. 2008. Identification of a novel splice variant of the haloacid dehalogenase: PHOSPHO1. Biochemical and Biophysical Research Communications. 371 (4), pp. 872-876. https://doi.org/10.1016/j.bbrc.2008.04.163
The growth plate sparing effects of the selective glucocorticoid receptor modulator, AL-438
Owen, H., Miner, J., Ahmed, S. and Farquharson, C. 2007. The growth plate sparing effects of the selective glucocorticoid receptor modulator, AL-438. Molecular and Cellular Endocrinology. 264 (1-2), pp. 164-70. https://doi.org/10.1016/j.mce.2006.11.006