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.
- low back pain
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JH and Q-JM are joint senior authors.
Handling editor Josef S Smolen
Contributors Q-JM and JH conceived the ideas of the review and were involved in writing and revising all sections. HM took the lead role in writing most sections of this review, and coordinated the sections contributed by other coauthors. CFG wrote the temperature entrainment section and designed all figures with inputs from other coauthors. MD wrote the mechanical loading section.
Funding Medical Research Council DTP PhD studentship to HM; Medical Research Council project grants MR/T016744/1 and MR/P010709/1 to Q-JM and JAH. RUBICON Secondment Fellowship EU project H2020‐MSCA‐RISE‐2015_69085 to HM. vs Arthritis Senior Research Fellowship Award 20 875 to Q-JM. Wellcome Trust for the WT Centre for Cell-Matrix Research 088785/Z/09; Wellcome Trust PhD studentship 215205/Z/19/Z to CFG.
Competing interests None declared.
Patient and public involvement Patients and/or the public were not involved in the design, or conduct, or reporting or dissemination plans of this research.
Provenance and peer review Not commissioned; externally peer reviewed.
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