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Microenvironmental mechanoactivation through Yap/Taz suppresses chondrogenic gene expression
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 chon...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The American Society for Cell Biology
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10295477/ https://www.ncbi.nlm.nih.gov/pubmed/37043309 http://dx.doi.org/10.1091/mbc.E22-12-0543 |
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author | Hallström, Grey F. Jones, Dakota L. Locke, Ryan C. Bonnevie, Edward D. Kim, Sung Yeon Laforest, Lorielle Garcia, Diana Cruz Mauck, Robert L. |
author_facet | Hallström, Grey F. Jones, Dakota L. Locke, Ryan C. Bonnevie, Edward D. Kim, Sung Yeon Laforest, Lorielle Garcia, Diana Cruz Mauck, Robert L. |
author_sort | Hallström, Grey F. |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-10295477 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | The American Society for Cell Biology |
record_format | MEDLINE/PubMed |
spelling | pubmed-102954772023-08-16 Microenvironmental mechanoactivation through Yap/Taz suppresses chondrogenic gene expression Hallström, Grey F. Jones, Dakota L. Locke, Ryan C. Bonnevie, Edward D. Kim, Sung Yeon Laforest, Lorielle Garcia, Diana Cruz Mauck, Robert L. Mol Biol Cell Articles 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. The American Society for Cell Biology 2023-06-01 /pmc/articles/PMC10295477/ /pubmed/37043309 http://dx.doi.org/10.1091/mbc.E22-12-0543 Text en © 2023 Hallström et al. “ASCB®,” “The American Society for Cell Biology®,” and “Molecular Biology of the Cell®” are registered trademarks of The American Society for Cell Biology. https://creativecommons.org/licenses/by-nc-sa/3.0/This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial-Share Alike 4.0 International Creative Commons License. |
spellingShingle | Articles Hallström, Grey F. Jones, Dakota L. Locke, Ryan C. Bonnevie, Edward D. Kim, Sung Yeon Laforest, Lorielle Garcia, Diana Cruz Mauck, Robert L. Microenvironmental mechanoactivation through Yap/Taz suppresses chondrogenic gene expression |
title | Microenvironmental mechanoactivation through Yap/Taz suppresses chondrogenic gene expression |
title_full | Microenvironmental mechanoactivation through Yap/Taz suppresses chondrogenic gene expression |
title_fullStr | Microenvironmental mechanoactivation through Yap/Taz suppresses chondrogenic gene expression |
title_full_unstemmed | Microenvironmental mechanoactivation through Yap/Taz suppresses chondrogenic gene expression |
title_short | Microenvironmental mechanoactivation through Yap/Taz suppresses chondrogenic gene expression |
title_sort | microenvironmental mechanoactivation through yap/taz suppresses chondrogenic gene expression |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10295477/ https://www.ncbi.nlm.nih.gov/pubmed/37043309 http://dx.doi.org/10.1091/mbc.E22-12-0543 |
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