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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.<\/jats:p>\n               <jats:p>This article has an associated First Person interview with the first author of the paper.<\/jats:p>","DOI":"10.1242\/jcs.247643","type":"journal-article","created":{"date-parts":[[2020,12,11]],"date-time":"2020-12-11T13:16:26Z","timestamp":1607692586000},"source":"Crossref","is-referenced-by-count":36,"title":["Hydrostatic pressure prevents chondrocyte differentiation through heterochromatin remodeling"],"prefix":"10.1242","volume":"134","author":[{"given":"Koichiro","family":"Maki","sequence":"first","affiliation":[{"name":"Helsinki Institute of Life Science, Biomedicum 1 , , 00290 Helsinki , Finland"},{"name":"University of Helsinki 1 , , 00290 Helsinki , Finland"},{"name":"Wihuri Research Institute, Biomedicum 2 , , 00290 Helsinki , Finland"},{"name":"University of Helsinki 2 , , 00290 Helsinki , Finland"},{"name":"Stem Cells and Metabolism Research Program 3 , Faculty of Medicine , , 00290 Helsinki , Finland"},{"name":"University of Helsinki 3 , Faculty of Medicine , , 00290 Helsinki , Finland"},{"name":"The University of Tokyo 4 Department of Mechanical Engineering , , Tokyo 113-0033 , Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michele M.","family":"Nava","sequence":"additional","affiliation":[{"name":"Helsinki Institute of Life Science, Biomedicum 1 , , 00290 Helsinki , Finland"},{"name":"University of Helsinki 1 , , 00290 Helsinki , Finland"},{"name":"Wihuri Research Institute, Biomedicum 2 , , 00290 Helsinki , Finland"},{"name":"University of Helsinki 2 , , 00290 Helsinki , Finland"},{"name":"Stem Cells and Metabolism Research Program 3 , Faculty of Medicine , , 00290 Helsinki , Finland"},{"name":"University of Helsinki 3 , Faculty of Medicine , , 00290 Helsinki , Finland"},{"name":"Max Planck Institute for Biology of Ageing 5 , 50931 Cologne , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cl\u00e9mentine","family":"Villeneuve","sequence":"additional","affiliation":[{"name":"Helsinki Institute of Life Science, Biomedicum 1 , , 00290 Helsinki , Finland"},{"name":"University of Helsinki 1 , , 00290 Helsinki , Finland"},{"name":"Wihuri Research Institute, Biomedicum 2 , , 00290 Helsinki , Finland"},{"name":"University of Helsinki 2 , , 00290 Helsinki , Finland"},{"name":"Stem Cells and Metabolism Research Program 3 , Faculty of Medicine , , 00290 Helsinki , Finland"},{"name":"University of Helsinki 3 , Faculty of Medicine , , 00290 Helsinki , Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Minki","family":"Chang","sequence":"additional","affiliation":[{"name":"The University of Tokyo 4 Department of Mechanical Engineering , , Tokyo 113-0033 , Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katsuko S.","family":"Furukawa","sequence":"additional","affiliation":[{"name":"The University of Tokyo 4 Department of Mechanical Engineering , , Tokyo 113-0033 , Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takashi","family":"Ushida","sequence":"additional","affiliation":[{"name":"The University of Tokyo 4 Department of Mechanical Engineering , , Tokyo 113-0033 , Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6383-6292","authenticated-orcid":false,"given":"Sara A.","family":"Wickstr\u00f6m","sequence":"additional","affiliation":[{"name":"Helsinki Institute of Life Science, Biomedicum 1 , , 00290 Helsinki , Finland"},{"name":"University of Helsinki 1 , , 00290 Helsinki , Finland"},{"name":"Wihuri Research Institute, Biomedicum 2 , , 00290 Helsinki , Finland"},{"name":"University of Helsinki 2 , , 00290 Helsinki , Finland"},{"name":"Stem Cells and Metabolism Research Program 3 , Faculty of Medicine , , 00290 Helsinki , Finland"},{"name":"University of Helsinki 3 , Faculty of Medicine , , 00290 Helsinki , Finland"},{"name":"Max Planck Institute for Biology of Ageing 5 , 50931 Cologne , Germany"},{"name":"Cologne Excellence Cluster for Stress Responses in Ageing-associated diseases (CECAD), University of Cologne 6 , 50931 Cologne , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","published-online":{"date-parts":[[2021,1,27]]},"reference":[{"key":"2024061307380478900_JCS247643C1","doi-asserted-by":"publisher","first-page":"445","DOI":"10.1016\/S0021-9290(98)00035-9","article-title":"Incompressibility of the solid matrix of articular cartilage under high hydrostatic pressures","volume":"31","author":"Bachrach","year":"1998","journal-title":"J. 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