University of Oulu

Matta, C., Lewis, R., Fellows, C., Diszhazi, G., Almassy, J., Miosge, N., Dixon, J., Uribe, M. C., May, S., Poliska, S., Barrett-Jolley, R., Fodor, J., Szentesi, P., Hajdú, T., Keller-Pinter, A., Henslee, E., Labeed, F. H., Hughes, M. P., & Mobasheri, A. (2021). Transcriptome-based screening of ion channels and transporters in a migratory chondroprogenitor cell line isolated from late-stage osteoarthritic cartilage. J Cell Physiol, 236, 7421– 7439. https://doi.org/10.1002/jcp.30413

Transcriptome-based screening of ion channels and transporters in a migratory chondroprogenitor cell line isolated from late-stage osteoarthritic cartilage

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Author: Matta, Csaba1,2; Lewis, Rebecca2; Fellows, Christopher2;
Organizations: 1Department of Anatomy, Histology and Embryology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary
2Department of Veterinary Preclinical Sciences, School of Veterinary Medicine, Faculty of Health and Medical Sciences, University of Surrey, Guildford, UK
3Department of Physiology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary
4Department of Prosthodontics, Tissue Regeneration Work Group, Georg August University, Göttingen, Germany
5Wolfson Centre for Stem Cells, Tissue Engineering and Modelling, Centre of Biomolecular Sciences, School of Pharmacy, University of Nottingham, Nottingham, UK
6The Nottingham Arabidopsis Stock Centre (NASC), School of Biosciences, University of Nottingham, Sutton Bonington Campus, Loughborough, UK
7Genomic Medicine and Bioinformatic Core Facility, Department of Biochemistry and Molecular Biology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary
8Department of Musculoskeletal Biology, Faculty of Health and Life Sciences, Institute of Ageing and Chronic Disease, University of Liverpool, Liverpool, UK
9Department of Biochemistry, Faculty of Medicine, University of Szeged, Szeged, Hungary
10Department of Mechanical Engineering Sciences, Centre for Biomedical Engineering, University of Surrey, Guildford, UK
11Department of Regenerative Medicine, State Research Institute Centre for Innovative Medicine, Vilnius, Lithuania
12Research Unit of Medical Imaging, Physics and Technology, Faculty of Medicine, University of Oulu, Oulu, Finland
13Departments of Orthopedics, Rheumatology and Clinical Immunology, University Medical Center Utrecht, Utrecht, The Netherlands
14Department of Joint Surgery, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 3.5 MB)
Persistent link: http://urn.fi/urn:nbn:fi-fe2021111555189
Language: English
Published: John Wiley & Sons, 2021
Publish Date: 2021-11-15
Description:

Abstract

Chondrogenic progenitor cells (CPCs) may be used as an alternative source of cells with potentially superior chondrogenic potential compared to mesenchymal stem cells (MSCs), and could be exploited for future regenerative therapies targeting articular cartilage in degenerative diseases such as osteoarthritis (OA). In this study, we hypothesised that CPCs derived from OA cartilage may be characterised by a distinct channelome. First, a global transcriptomic analysis using Affymetrix microarrays was performed. We studied the profiles of those ion channels and transporter families that may be relevant to chondroprogenitor cell physiology. Following validation of the microarray data with quantitative reverse transcription-polymerase chain reaction, we examined the role of calcium-dependent potassium channels in CPCs and observed functional large-conductance calcium-activated potassium (BK) channels involved in the maintenance of the chondroprogenitor phenotype. In line with our very recent results, we found that the KCNMA1 gene was upregulated in CPCs and observed currents that could be attributed to the BK channel. The BK channel inhibitor paxilline significantly inhibited proliferation, increased the expression of the osteogenic transcription factor RUNX2, enhanced the migration parameters, and completely abolished spontaneous Ca2+ events in CPCs. Through characterisation of their channelome we demonstrate that CPCs are a distinct cell population but are highly similar to MSCs in many respects. This study adds key mechanistic data to the in-depth characterisation of CPCs and their phenotype in the context of cartilage regeneration.

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Series: Journal of cellular physiology
ISSN: 0021-9541
ISSN-E: 1097-4652
ISSN-L: 0021-9541
Volume: 236
Issue: 11
Pages: 7421 - 7439
DOI: 10.1002/jcp.30413
OADOI: https://oadoi.org/10.1002/jcp.30413
Type of Publication: A1 Journal article – refereed
Field of Science: 1182 Biochemistry, cell and molecular biology
3121 General medicine, internal medicine and other clinical medicine
Subjects:
Funding: Csaba Matta was supported by the European Commission through a Marie Skłodowska-Curie Intra-European Fellowship for career development (Project no. 625746; acronym: CHONDRION; FP7-PEOPLE-2013-IEF), the Premium Postdoctoral Research Fellowship of the Eötvös Loránd Research Network (ELKH) and the Young Researcher Excellence Programme (Grant no. FK 134304) of the National Research, Development and Innovation Office, Hungary. Project no. TKP2020-NKA-04 has been implemented with the support provided by the National Research, Development and Innovation Fund of Hungary, financed under the 2020-4.1.1-TKP2020 funding scheme. Ali Mobasheri was the coordinator of the D-BOARD Consortium funded by European Commission Framework 7 programme (EU FP7; HEALTH.2012.2.4.5-2; Project no. 305815; Novel Diagnostics and Biomarkers for Early Identification of Chronic Inflammatory Joint Diseases). Ali Mobasheri has received funding from the Deanship of Scientific Research (DSR), King AbdulAziz University (Grant no. 1-141/1434 HiCi). Ali Mobasheri is a member of the Arthritis Research UK Centre for Sport, Exercise and Osteoarthritis, funded by Arthritis Research UK (Grant Reference no. 20194). Ali Mobasheri wishes to acknowledge financial support from the European Structural and Social Funds (ES Struktūrinės Paramos) through the Research Council of Lithuania (Lietuvos Mokslo Taryba) according to the activity ‘Improvement of researchers’ qualification by implementing world-class R&D projects' of Measure no. 09.3.3-LMT-K-712 (Grant application code: 09.3.3-LMT-K-712-01-0157; Agreement no. DOTSUT-215) and the new funding programme: Attracting Foreign Researchers for Research Implementation (2018–2022), Grant no. 01.2.2-LMT-K-718-02-0022. Aniko Keller-Pinter was supported by the National Research, Development and Innovation Office of Hungary (Grant no. FK 134684), and by the GINOP-2.3.2-15-2016-00040 project.
Copyright information: © 2021 The Authors. Journal of Cellular Physiology published by Wiley Periodicals LLC. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
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