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Tissue physiology revolving around the clock: circadian rhythms as exemplified by the intervertebral disc.

Authors
  • Morris, Honor1, 2
  • Gonçalves, Cátia F1, 2
  • Dudek, Michal1, 2
  • Hoyland, Judith3, 4
  • Meng, Qing-Jun5, 2
  • 1 Wellcome Centre for Cell Matrix Research, University of Manchester, Manchester, UK.
  • 2 Division of Cell Matrix Biology and Regenerative Medicine, School of Biological Sciences, University of Manchester, Manchester, UK.
  • 3 Division of Cell Matrix Biology and Regenerative Medicine, School of Biological Sciences, University of Manchester, Manchester, UK [email protected] [email protected]
  • 4 NIHR Manchester Musculoskeletal Biomedical Research Centre, Manchester University, NHS Foundation Trust, Manchester Academic Health Science Centre, University of Manchester, Manchester, UK.
  • 5 Wellcome Centre for Cell Matrix Research, University of Manchester, Manchester, UK [email protected] [email protected]
Type
Published Article
Journal
Annals of the Rheumatic Diseases
Publisher
BMJ
Publication Date
Jul 01, 2021
Volume
80
Issue
7
Pages
828–839
Identifiers
DOI: 10.1136/annrheumdis-2020-219515
PMID: 33397731
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

Circadian clocks in the brain and peripheral tissues temporally coordinate local physiology to align with the 24 hours rhythmic environment through light/darkness, rest/activity and feeding/fasting cycles. Circadian disruptions (during ageing, shift work and jet-lag) have been proposed as a risk factor for degeneration and disease of tissues, including the musculoskeletal system. The intervertebral disc (IVD) in the spine separates the bony vertebrae and permits movement of the spinal column. IVD degeneration is highly prevalent among the ageing population and is a leading cause of lower back pain. The IVD is known to experience diurnal changes in loading patterns driven by the circadian rhythm in rest/activity cycles. In recent years, emerging evidence indicates the existence of molecular circadian clocks within the IVD, disruption to which accelerates tissue ageing and predispose animals to IVD degeneration. The cell-intrinsic circadian clocks in the IVD control key aspects of physiology and pathophysiology by rhythmically regulating the expression of ~3.5% of the IVD transcriptome, allowing cells to cope with the drastic biomechanical and chemical changes that occur throughout the day. Indeed, epidemiological studies on long-term shift workers have shown an increased incidence of lower back pain. In this review, we summarise recent findings of circadian rhythms in health and disease, with the IVD as an exemplar tissue system. We focus on rhythmic IVD functions and discuss implications of utilising biological timing mechanisms to improve tissue health and mitigate degeneration. These findings may have broader implications in chronic rheumatic conditions, given the recent findings of musculoskeletal circadian clocks. © Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.

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