Logo image
Back
Microenvironmental mechanoactivation through Yap/Taz suppresses chondrogenic gene expression
Journal article   Peer reviewed

Microenvironmental mechanoactivation through Yap/Taz suppresses chondrogenic gene expression

Grey F. Hallström, Dakota L. Jones, Ryan C. Locke, Edward D. Bonnevie, Sung Yeon Kim, Lorielle Laforest, Diana Cruz Garcia and Robert L. Mauck
Molecular biology of the cell, Vol.34(7), p.ar73
06/01/2023
DOI: 10.1091/mbc.E22-12-0543
PMCID: PMC10295477
PMID: 37043309
url
https://pmc.ncbi.nlm.nih.gov/articles/PMC10295477/pdf/mbc-34-ar73.pdfView
Open Access

Abstract

Chondrocyte phenotype is regulated, in part, by Rho signaling. Rho can relay mechanical signals through increased activation of Yap, a transcriptional co-regulator. Here we demonstrate that Yap nuclear translocation downstream of Rho activation is essential for suppressing chondrogenesis. Chondrocyte phenotype is preserved when cells are round and the actin cytoskeleton is cortical. Conversely, these cells rapidly dedifferentiate in vitro with increased mechanoactive Rho signaling, which increases cell size and causes large actin stress fiber to form. While the effects of Rho on chondrocyte phenotype are well established, the molecular mechanism is not yet fully elucidated. Yap, a transcriptional coregulator, is regulated by Rho in a mechanotransductive manner and can suppress chondrogenesis in vivo. Here, we sought to elucidate the relationship between mechanoactive Rho and Yap on chondrogenic gene expression. We first show that decreasing mechanoactive state through Rho inhibition results in a broad increase in chondrogenic gene expression. Next, we show that Yap and its coregulator Taz are negative regulators of chondrogenic gene expression, and removal of these factors promotes chondrogenesis even in environments that promote cell spreading. Finally, we establish that Yap/Taz is essential for translating Rho-mediated signals to negatively regulate chondrogenic gene expression, and that its removal negates the effects of increased Rho signaling. Together, these data indicate that Rho is a mechanoregulator of chondrogenic differentiation, and that its impact on chondrogenic expression is exerted principally through mechanically induced translocation and activity of Yap and Taz.

Details

Metrics

4 Record Views
Logo image