Journal
JOURNAL OF CELL SCIENCE
Volume 134, Issue 2, Pages -Publisher
COMPANY BIOLOGISTS LTD
DOI: 10.1242/jcs.247643
Keywords
Chondrocyte; Differentiation; Heterochromatin; Hydrostatic pressure; Mechanotransduction; Nucleus; Replicative stress
Categories
Funding
- Academy of Finland [317597]
- Max Planck Society
- Japan Society for the Promotion of Science (JSPS) KAKENHI [17J03032]
- Nakatomi Foundation
- Yamada Science Foundation
- JSPS KAKENHI [15H01800]
- ERC under the European Union's Horizon 2020 research and innovation programme (Marie Sklodowska-Curie Actions) [748004]
- Helsinki Institute of Life Science
- Wihuri Research Institute
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The study reveals that hydrostatic pressure promotes chondrocyte quiescence and prevents maturation towards the hypertrophic state by triggering chromatin remodeling, impacting cell fate and function.
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 hyperlrophic 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.
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