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Reduced telomere length is associated with fibrotic joint disease suggesting that impaired telomere repair contributes to joint fibrosis

Lookup NU author(s): Dr Nicholas Kalson, Timothy Brock, Professor Derek Mann, Dr Lee Borthwick, Professor David Deehan

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This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


Abstract

© 2018 Kalson et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Objective Joint fibrosis affects many synovial joints (including hip, knee and shoulder) causing stiffness and pain. The mechanism of joint fibrosis remains unknown, although genetic factors may contribute. Defects in maintenance of telomere length resulting from impaired telomere repair have been shown to cause lung and liver fibrotic disease. Here we tested the hypothesis that joint fibrosis and other soft tissue fibrotic conditions are also associated with telomere length. Patients and methods 5,200 participants in the TwinsUK registry had data on telomere length (measured by qPCR) and the traits of interest (hip and knee stiffness, total joint replacement (TJR, hip or knee) and fibrotic conditions (Dupuytren’s disease, frozen shoulder). Results Multivariable logistic regression analyses showed a significant association between telomere length and fibrotic conditions (hip stiffness, knee stiffness and frozen shoulder, p = 0.002) even after taking age into account. No association was found between TJR and telomere length. Conclusion These findings suggest that defects in telomere repair contribute to joint fibrosis, and that fibrosis shares a common mechanistic pathway in different organs. Therapeutic strategies to combat telomere shortening may offer novel treatments for fibrotic joint disease.


Publication metadata

Author(s): Kalson NS, Brock TM, Mangino M, Fabiane SM, Mann DA, Borthwick LA, Deehan DJ, Williams FMK

Publication type: Article

Publication status: Published

Journal: PLoS ONE

Year: 2018

Volume: 13

Issue: 1

Online publication date: 02/01/2018

Acceptance date: 20/11/2017

ISSN (electronic): 1932-6203

Publisher: Public Library of Science

URL: https://doi.org/10.1371/journal.pone.0190120

DOI: 10.1371/journal.pone.0190120


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