Transient receptor potential vanilloid 4 as a regulator of induced pluripotent stem cell chondrogenesis

As induced pluripotent stem cells (iPSCs) undergo chondrogenesis,Trpv4 expression mirrored the expression of other chondrogenic markers (eg,Sox9,Acan, andCol2a1). Using aCol2a1-GFP reporter, green fluorescent protein positive (GFP+) cells showed increased chondrogenesis and expression ofTrpv4. Daily activation of transient receptor potential vanilloid 4 (TRPV4) significantly increased cartilaginous matrix production in GFP+ cells. These findings suggest that TRPV4 serves as a marker as well as a regulator of iPSC chondrogenesis. AbstractTransient receptor potential vanilloid 4 (TRPV4) is a polymodal calcium-permeable cation channel that is highly expressed in cartilage and is sensitive to a variety of extracellular stimuli. The expression of this channel has been associated with the process of chondrogenesis in adult stem cells as well as several cell lines. Here, we used a chondrogenic reporter (Col2a1-GFP) in murine induced pluripotent stem cells (iPSCs) to examine the hypothesis that TRPV4 serves as both a marker and a regulator of chondrogenesis. Over 21  days of chondrogenesis, iPSCs showed significant increases inTrpv4 expression along with the standard chondrogenic gene markersSox9,Acan, andCol2a1, particularly in the green fluorescent protein positive (GFP+) chondroprogenitor subpopulation. Increased gene expression forTrpv4 was also reflected by the presence of TRPV4 protein and functional Ca2+ signaling. Daily activation of TRPV4 using the specific agonist GSK1016...
Source: Stem Cells - Category: Stem Cells Authors: Tags: Embryonic Stem Cells/Induced Pluripotent Stem Cells Source Type: research