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

• Published in: Journal of cellular physiology Vol. 236; no. 11; pp. 7421 - 7439
• Main Authors: Matta, Csaba, Lewis, Rebecca, Fellows, Christopher, Diszhazi, Gyula, Almassy, Janos, Miosge, Nicolai, Dixon, James, Uribe, Marcos C., May, Sean, Poliska, Szilard, Barrett‐Jolley, Richard, Fodor, Janos, Szentesi, Peter, Hajdú, Tibor, Keller‐Pinter, Aniko, Henslee, Erin, Labeed, Fatima H., Hughes, Michael P., Mobasheri, Ali
• Format: Journal Article
• Language: English
• Published: United States Wiley Subscription Services, Inc 01.11.2021
• Subjects: Biomedical materials; Calcium; Calcium channels; Calcium conductance; Calcium ions; Calcium Signaling; Cartilage; Cartilage (articular); Cartilage diseases; Cartilage, Articular - drug effects; Cartilage, Articular - metabolism; Cartilage, Articular - pathology; Cbfa-1 protein; Cell Line; Cell migration; Cell Movement - drug effects; Cell Proliferation; channelome; chondrocyte; Chondrocytes - drug effects; Chondrocytes - metabolism; Chondrocytes - pathology; chondroprogenitor; Core Binding Factor Alpha 1 Subunit - genetics; Core Binding Factor Alpha 1 Subunit - metabolism; DNA microarrays; Gene Expression Profiling; Humans; Ion channels; Ion Channels - genetics; Ion Channels - metabolism; Large-Conductance Calcium-Activated Potassium Channel alpha Subunits - genetics; Large-Conductance Calcium-Activated Potassium Channel alpha Subunits - metabolism; Membrane Potentials; Membrane Transport Proteins - genetics; Membrane Transport Proteins - metabolism; mesenchymal stem cell; Mesenchyme; Osteoarthritis; Osteoarthritis, Knee - genetics; Osteoarthritis, Knee - metabolism; Osteoarthritis, Knee - pathology; Osteoprogenitor cells; Phenotypes; Polymerase chain reaction; Potassium; Potassium Channel Blockers - pharmacology; Potassium channels; Potassium conductance; Progenitor cells; Regeneration; Reverse transcription; Stem cells; Stem Cells - drug effects; Stem Cells - metabolism; Stem Cells - pathology; Time Factors; Transcriptome; Transcriptomes; transcriptomics; chondroprogenitor; mesenchymal stem cell; chondrocyte; osteoarthritis; cartilage; transcriptomics; channelome
• ISSN: 0021-9541; 1097-4652
• DOI: 10.1002/jcp.30413

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. 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 analysed the channelome of CPCs and MSCs using Affymetrix microarrays and 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. We demonstrate that CPCs are a distinct cell population but are highly similar to MSCs in many respects.