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Lookup NU author(s): Dr Matthew BarterORCiD, Adam Farrier, Dr Andreas Panagiotopoulos, Professor David Deehan, Dr Louise ReynardORCiD, Professor David YoungORCiD
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
© 2026 The AuthorsObjective: Cell type-specific gene expression programs are mediated by interactions between enhancers, transcription factors and gene promoters. Access to the DNA is regulated by the presence and modification state of chromatin. This study sought to reveal the chromatin accessibility of the cartilage chondrocyte genome and identify changes that occur in accessibility during both development from mesenchymal stem cells (MSC) and in osteoarthritis (OA). Method: Assay for Transposase-Accessible Chromatin using Sequencing (ATAC-seq) was performed on bone-marrow-MSC and MSC-derived differentiated chondrocytes, as well as primary chondrocytes isolated from 16 patients undergoing total hip replacement because of OA or due to a neck of femur fracture. Results: During MSC chondrogenesis we identified 138,005 open chromatin regions, with 20,979 regions undergoing increased accessibility. De novo established accessible regions were enriched at enhancer regions, defined previously by ChIP-seq, with key cartilage genes experiencing substantial chromatin reconfiguration often overlapping with SOX9 binding sites. In hip chondrocytes we identified 115,295 open chromatin regions, of which 1383 and 573 were more or less differentially accessible in OA. Comparison with a single cell ATAC-seq ATLAS identified accessible regions restricted to chondrocytes and established during chondrogenesis. Accessible regions were mapped to 320 OA-associated single nucleotide variants, many of which become accessible during chondrocyte development. Conclusions: This study illustrates the establishment of the chondrocyte chromatin landscape and identifies enhancer regions correlated with the cartilage transcriptome and associated with variants linked with cartilage disease OA.
Author(s): Barter MJ, Soul J, Cheung K, Falk J, Putri K, Farrier AJ, Panagiotopoulos A, Deehan DJ, Reynard LN, Young DA
Publication type: Article
Publication status: Published
Journal: Osteoarthritis and Cartilage
Year: 2026
Pages: epub ahead of print
Online publication date: 07/01/2026
Acceptance date: 11/12/2025
Date deposited: 09/02/2026
ISSN (print): 1063-4584
ISSN (electronic): 1522-9653
Publisher: Elsevier
URL: https://doi.org/10.1016/j.joca.2025.12.015
DOI: 10.1016/j.joca.2025.12.015
PubMed id: 41512915
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