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Hydrostatic pressure prevents chondrocyte differentiation through heterochromatin remodeling.

Authors
  • Maki, Koichiro1, 2, 3, 4
  • Nava, Michele M1, 2, 3, 5
  • Villeneuve, Clémentine1, 2, 3
  • Chang, Minki4
  • Furukawa, Katsuko S4
  • Ushida, Takashi4
  • Wickström, Sara A6, 2, 3, 5, 7
  • 1 Helsinki Institute of Life Science, Biomedicum, University of Helsinki, 00290 Helsinki, Finland. , (Finland)
  • 2 Wihuri Research Institute, Biomedicum, University of Helsinki, 00290 Helsinki, Finland. , (Finland)
  • 3 Stem Cells and Metabolism Research Program, Faculty of Medicine, University of Helsinki, 00290 Helsinki, Finland. , (Finland)
  • 4 Department of Mechanical Engineering, The University of Tokyo, Tokyo 113-0033, Japan. , (Japan)
  • 5 Max Planck Institute for Biology of Ageing, 50931 Cologne, Germany. , (Germany)
  • 6 Helsinki Institute of Life Science, Biomedicum, University of Helsinki, 00290 Helsinki, Finland [email protected] , (Finland)
  • 7 Cologne Excellence Cluster for Stress Responses in Ageing-associated diseases (CECAD), University of Cologne, 50931 Cologne, Germany. , (Germany)
Type
Published Article
Journal
Journal of Cell Science
Publisher
The Company of Biologists
Publication Date
Jan 27, 2021
Volume
134
Issue
2
Identifiers
DOI: 10.1242/jcs.247643
PMID: 33310912
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

Articular cartilage protects and lubricates joints for smooth motion and transmission of loads. Owing to its high water content, chondrocytes within the cartilage are exposed to high levels of hydrostatic pressure, which has been shown to promote chondrocyte identity through unknown mechanisms. Here, we investigate the effects of hydrostatic pressure on chondrocyte state and behavior, and discover that application of hydrostatic pressure promotes chondrocyte quiescence and prevents maturation towards the hypertrophic state. Mechanistically, hydrostatic pressure reduces the amount of trimethylated H3K9 (K3K9me3)-marked constitutive heterochromatin and concomitantly increases H3K27me3-marked facultative heterochromatin. Reduced levels of H3K9me3 attenuates expression of pre-hypertrophic genes, replication and transcription, thereby reducing replicative stress. Conversely, promoting replicative stress by inhibition of topoisomerase II decreases Sox9 expression, suggesting that it enhances chondrocyte maturation. Our results reveal how hydrostatic pressure triggers chromatin remodeling to impact cell fate and function.This article has an associated First Person interview with the first author of the paper. © 2021. Published by The Company of Biologists Ltd.

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