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

Vincent P. Willard, Holly A. Leddy, Daniel Palmer, Chia Lung Wu, Wolfgang Liedtke, Farshid Guilak

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

Transient 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 in Trpv4 expression along with the standard chondrogenic gene markers Sox9, Acan, and Col2a1, particularly in the green fluorescent protein positive (GFP+) chondroprogenitor subpopulation. Increased gene expression for Trpv4 was also reflected by the presence of TRPV4 protein and functional Ca2+ signaling. Daily activation of TRPV4 using the specific agonist GSK1016790A resulted in significant increases in cartilaginous matrix production. An improved understanding of the role of TRPV4 in chondrogenesis may provide new insights into the development of new therapeutic approaches for diseases of cartilage, such as osteoarthritis, or channelopathies and hereditary disorders that affect cartilage during development. Harnessing the role of TRPV4 in chondrogenesis may also provide a novel approach for accelerating stem cell differentiation in functional tissue engineering of cartilage replacements for joint repair.

Original languageEnglish
Pages (from-to)1447-1456
Number of pages10
JournalSTEM CELLS
Volume39
Issue number11
DOIs
StatePublished - Nov 2021

Keywords

  • TRP channel
  • adipose stem cell
  • hypertrophy
  • mesenchymal stem cell
  • tissue engineering

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