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Oxygen and reactive oxygen species in articular cartilage: modulators of ionic homeostasis

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Abstract

Articular cartilage is an avascular tissue dependent on diffusion mainly from synovial fluid to service its metabolic requirements. Levels of oxygen (O2) in the tissue are low, with estimates of between 1 and 6%. Metabolism is largely, if not entirely, glycolytic, with little capacity for oxidative phosphorylation. Notwithstanding, the tissue requires O2 and consumes it, albeit at low rates. Changes in O2 tension also have profound effects on chondrocytes affecting phenotype, gene expression, and morphology, as well as response to, and production of, cytokines. Although chondrocytes can survive prolonged anoxia, low O2 levels have significant metabolic effects, inhibiting glycolysis (the negative Pasteur effect), and also notably matrix production. Why this tissue should respond so markedly to reduction in O2 tension remains a paradox. Ion homeostasis in articular chondrocytes is also markedly affected by the extracellular matrix in which the cells reside. Recent work has shown that ion homeostasis also responds to changes in O2 tension, in such a way as to produce significant effects on cell function. For this purpose, O2 probably acts via alteration in levels of reactive oxygen species. We discuss the possibility that O2 consumption by this tissue is required to maintain levels of ROS, which are then used physiologically as an intracellular signalling device. This postulate may go some way towards explaining why the tissue is dependent on O2 and why its removal has such marked effects. Understanding the role of oxygen has implications for disease states in which O2 or ROS levels may be perturbed.

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Acknowledgement

We are grateful for financial support from the BBSRC, the Royal Society and the Sir Halley Stewart Trust. During this work, PIM was funded at Cambridge by a Veterinary Research Training Scholarship from the Horserace Betting Levy Board.

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Authors and Affiliations

  1. Department of Veterinary Medicine, University of Cambridge, Madingley Road, Cambridge, CB3 0ES, England

    J. S. Gibson & R. White

  2. Faculty of Veterinary Science, University of Liverpool, Neston, Cheshire, CH64 7TE, England

    P. I. Milner

  3. Department of Physiology, Anatomy and Genetics, University of Oxford, Sherrington Building, Parks Road, Oxford, OX1 3PT, England

    T. P. A. Fairfax & R. J. Wilkins

Authors
  1. J. S. Gibson
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  2. P. I. Milner
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  3. R. White
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  4. T. P. A. Fairfax
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  5. R. J. Wilkins
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Corresponding author

Correspondence to R. J. Wilkins.

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Gibson, J.S., Milner, P.I., White, R. et al. Oxygen and reactive oxygen species in articular cartilage: modulators of ionic homeostasis. Pflugers Arch - Eur J Physiol 455, 563–573 (2008). https://doi.org/10.1007/s00424-007-0310-7

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  • DOI: https://doi.org/10.1007/s00424-007-0310-7

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