Characterization of Histone Modifications in Late-Stage Rotator Cuff Tendinopathy

Kayleigh J. A. Orchard, Moeed Akbar, Lindsay A. N. Crowe, John Cole, Neal L. Millar, Stuart M. Raleigh

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    The development and progression of rotator cuff tendinopathy (RCT) is multifactorial and likely to manifest through a combination of extrinsic, intrinsic, and environmental factors, including genetics and epigenetics. However, the role of epigenetics in RCT, including the role of histone modification, is not well established. Using chromatin immunoprecipitation sequencing, differences in the trimethylation status of H3K4 and H3K27 histones in late-stage RCT compared to control were investigated in this study. For H3K4, 24 genomic loci were found to be significantly more trimethylated in RCT compared to control (p < 0.05), implicating genes such as DKK2, JAG2, and SMOC2 in RCT. For H3K27, 31 loci were shown to be more trimethylated (p < 0.05) in RCT compared to control, inferring a role for EPHA3, ROCK1, and DEFβ115. Furthermore, 14 loci were significantly less trimethylated (p < 0.05) in control compared to RCT, implicating EFNA5, GDF6, and GDF7. Finally, the TGFβ signaling, axon guidance, and regulation of focal adhesion assembly pathways were found to be enriched in RCT. These findings suggest that the development and progression of RCT is, at least in part, under epigenetic control, highlighting the influence of histone modifications in this disorder and paving the way to further understand the role of epigenome in RCT.
    Original languageEnglish
    Article number496
    Number of pages12
    Issue number2
    Early online date15 Feb 2023
    Publication statusE-pub ahead of print - 15 Feb 2023

    Bibliographical note

    Copyright: © 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// 4.0/).


    • Article
    • rotator cuff tendinopathy
    • epigenetics
    • histone modifications
    • chromatin immunoprecipitation
    • extracellular matrix
    • inflammation


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