Universität zu Köln

Maki, Koichiro, Nava, Michele M., Villeneuve, Clementine, Chang, Minki, Furukawa, Katsuko S., Ushida, Takashi and Wickstrom, Sara A. (2021). Hydrostatic pressure prevents chondrocyte differentiation through heterochromatin remodeling. J. Cell Sci., 134 (2). CAMBRIDGE: COMPANY BIOLOGISTS LTD. ISSN 1477-9137

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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 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.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Maki, Koichiro UNSPECIFIED UNSPECIFIED UNSPECIFIED Nava, Michele M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Villeneuve, Clementine UNSPECIFIED UNSPECIFIED UNSPECIFIED Chang, Minki UNSPECIFIED UNSPECIFIED UNSPECIFIED Furukawa, Katsuko S. UNSPECIFIED UNSPECIFIED UNSPECIFIED Ushida, Takashi UNSPECIFIED UNSPECIFIED UNSPECIFIED Wickstrom, Sara A. UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-592569
DOI:	10.1242/jcs.247643
Journal or Publication Title:	J. Cell Sci.
Volume:	134
Number:	2
Date:	2021
Publisher:	COMPANY BIOLOGISTS LTD
Place of Publication:	CAMBRIDGE
ISSN:	1477-9137
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language DOUBLE-STRAND BREAKS; ARTICULAR-CARTILAGE; TRANSCRIPTION FACTORS; PROGENITOR CELLS; SOX9; REPLICATION; METHYLATION; POLYCOMB; DYNAMICS; REVEALS Multiple languages Cell Biology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/59256