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The brain–joint axis in osteoarthritis: nerves, circadian clocks and beyond

Nature Reviews Rheumatology volume 12, pages 508516 (2016) | Download Citation

Abstract

Osteoarthritis (OA) is a prevalent and debilitating joint disease for which ageing, obesity and chronic inflammation are known risk factors. The central, peripheral and autonomic nervous systems are essential in all metabolic systems, and emerging evidence suggests a role for these systems in OA. In the past few years, metabolic diseases, such as obesity or diabetes, have been linked to disruption of circadian rhythms that are tightly regulated by the nervous system, whereas inflammatory and autoimmune diseases are known to be linked to disruption of the cholinergic vagus nerve reflex. Interestingly, metabolism, inflammation and circadian rhythms have all been linked to the development and progression of OA. This article reviews current knowledge of the direct and indirect roles of the nervous system and circadian system in the initiation and/or progression of OA, and highlights the directions for future research in this emerging field.

Key points

  • Osteoarthritis (OA) is an active disease of the whole joint that is subject to both local and systemic regulation

  • The nervous system controls key aspects of joint pathophysiology by regulating circadian rhythms, the hypothalamic–pituitary–adrenal axis, and metabolic and inflammatory pathways

  • Ageing, obesity and chronic inflammation interfere with the brain–joint axis (including the circadian system), which compromises joint homeostasis and increases susceptibility to OA

  • Circadian clocks in the central brain and peripheral joint tissues temporally coordinate local physiology to the daily rhythmic environment (light–dark, feeding–fasting, body temperature regulation and mechanical loading cycles)

  • Environmental or genetic disruption to the biological timing system might be a novel risk factor for OA susceptibility

  • Targeting the nervous system or circadian system could provide novel therapeutic avenues for OA

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Acknowledgements

F.B.'s work is supported by the Arthritis Foundation R&D (ROAD: Research on Osteoarthritic Diseases) and by the French Society of Rheumatology. Q.-J.M's work is supported by Arthritis Research UK and the Medical Research Council (UK).

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Affiliations

  1. Rheumatology Department, Sorbonnes Universités UPMC Univ Paris 06, INSERM UMRS_938, DHU i2B, Assistance Publique-Hopitaux de Paris, Hôpital Saint-Antoine, 184 rue du Faubourg Saint-Antoine, Paris 75012, France.

    • Francis Berenbaum
  2. Faculty of Biology, Medicine and Health, Wellcome Trust Centre for Cell Matrix Research, University of Manchester, Oxford Road, Manchester M13 9PT, UK. University of Manchester

    • Qing-Jun Meng

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Contributions

F.B. and Q.-J.M. researched the data for the article, contributed equally to discussions of its content, wrote the manuscript, and undertook review or editing of the manuscript before submission.

Competing interests

The authors declare no competing financial interests.

Corresponding authors

Correspondence to Francis Berenbaum or Qing-Jun Meng.

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https://doi.org/10.1038/nrrheum.2016.93

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