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

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,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.

Ca2+-Activated K+ Channels in Progenitor Cells of Musculoskeletal Tissues: A Narrative Review

“…During chondrogenic differentiation, undifferentiated progenitor cells undergo a series of events to give rise to cartilage-ECM-producing chondroblasts and chondrocytes [ 21 , 22 ]. Chondrogenic differentiation involves gradual changes in the transcriptome, the proteome, and the electrome (i.e., the totality of all ionic currents) of the cells as they progress to more mature phenotypes [ 23 ]. Nearly all channels and transporters that mediate ionic currents across the plasma membrane of mature chondrocytes have been observed in CPCs as well, some of which exhibit interesting expression patterns and unique roles.…”

“…We detected the protein level expression of K + channel subunits (KCMA1, KCNJ2, KCNQ2); Ca 2+ channel subunits (CA2D1, CA2D2, CA2D4, CAC1C, CAC1E, CAC1H); volume-regulated anion channel subunits (LRC8A, LRC8C, LRC8D); the mechanosensitive cation channel Piezo1; the TRPM2 and TRPM4 cation channels; and the VDAC1, VDAC2, and VDAC3 voltage-dependent anion-selective channels. We also carried out a transcript-level screening of ion channels and transporters in the same CPC cell line and established the composition of its channelome at the mRNA level [ 23 ]. Such global approaches are important for understanding the complexity of ionic currents in CPCs.…”

“…In a transcriptome-based screening, we observed the mRNA expression profiles for BK, IK, and SK channel subunits in CPCs [ 23 ]. According to the Affymetrix microarray transcriptome analysis, KCNMA1 (BK) and KCNN4 (IK) were upregulated in CPCs compared to MSCs, whereas KCNN3 (SK) was unchanged.…”

“…Paxilline treatment significantly increased the fibronectin-guided and random migration parameters of CPCs. These data indicated that BK channels may play an inhibitory role in migratory CPCs [ 23 ].…”

“…This model involves BK channels, L-type, voltage-gated Ca 2+ channels (Ca v 1.2), the non-voltage dependent epithelial Na + channel, and the Na + /Ca 2+ exchanger (NCX), which have all been shown to be essential for Ca 2+ oscillations [ 23 , 39 , 40 , 146 , 184 , 186 , 187 ]. In addition, the role of the “leak” K + channel TASK-2 and some voltage-gated delayed rectifier K + channels (K V 1.1, 4.1, and 1.3) is also considered [ 4 , 50 , 145 ].…”