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

Publication ,  Journal Article
Willard, VP; Leddy, HA; Palmer, D; Wu, C-L; Liedtke, W; Guilak, F
Published in: Stem Cells
November 2021

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.

Duke Scholars

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Published In

Stem Cells

DOI

EISSN

1549-4918

Publication Date

November 2021

Volume

39

Issue

11

Start / End Page

1447 / 1456

Location

England

Related Subject Headings

  • TRPV Cation Channels
  • Mice
  • Induced Pluripotent Stem Cells
  • Immunology
  • Chondrogenesis
  • Chondrocytes
  • Cells, Cultured
  • Cell Differentiation
  • Cartilage
  • Animals
 

Citation

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Willard, V. P., Leddy, H. A., Palmer, D., Wu, C.-L., Liedtke, W., & Guilak, F. (2021). Transient receptor potential vanilloid 4 as a regulator of induced pluripotent stem cell chondrogenesis. Stem Cells, 39(11), 1447–1456. https://doi.org/10.1002/stem.3440
Willard, Vincent P., Holly A. Leddy, Daniel Palmer, Chia-Lung Wu, Wolfgang Liedtke, and Farshid Guilak. “Transient receptor potential vanilloid 4 as a regulator of induced pluripotent stem cell chondrogenesis.Stem Cells 39, no. 11 (November 2021): 1447–56. https://doi.org/10.1002/stem.3440.
Willard VP, Leddy HA, Palmer D, Wu C-L, Liedtke W, Guilak F. Transient receptor potential vanilloid 4 as a regulator of induced pluripotent stem cell chondrogenesis. Stem Cells. 2021 Nov;39(11):1447–56.
Willard, Vincent P., et al. “Transient receptor potential vanilloid 4 as a regulator of induced pluripotent stem cell chondrogenesis.Stem Cells, vol. 39, no. 11, Nov. 2021, pp. 1447–56. Pubmed, doi:10.1002/stem.3440.
Willard VP, Leddy HA, Palmer D, Wu C-L, Liedtke W, Guilak F. Transient receptor potential vanilloid 4 as a regulator of induced pluripotent stem cell chondrogenesis. Stem Cells. 2021 Nov;39(11):1447–1456.
Journal cover image

Published In

Stem Cells

DOI

EISSN

1549-4918

Publication Date

November 2021

Volume

39

Issue

11

Start / End Page

1447 / 1456

Location

England

Related Subject Headings

  • TRPV Cation Channels
  • Mice
  • Induced Pluripotent Stem Cells
  • Immunology
  • Chondrogenesis
  • Chondrocytes
  • Cells, Cultured
  • Cell Differentiation
  • Cartilage
  • Animals