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Hypoxia and HIF-1α in osteoarthritis

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Abstract

We have previously shown that functional inactivation of hypoxia-inducible factor-1α (HIF-1α) in growth-plate chondrocytes will dramatically inhibit anaerobic energy generation and matrix synthesis. Using immunohistochemistry, we have now analyzed the spatial distribution of HIF-1α and its target genes in normal cartilage and in cartilage from knee joints with osteoarthritis. We detected HIF-1α and its target genes in both types of cartilage. In cartilage from joints with osteoarthritis, the number of HIF-1α-, Glut-1-, and PGK-1-stained chondrocytes increased with the severity of osteoarthritis. Activated matrix synthesis and strongly decreased oxygen levels are hallmarks of osteoarthritic cartilage. Thus, we assume that chondrocytes are depending on the adaptive functions of HIF-1α in order to maintain ATP levels and thereby matrix synthesis during the course of osteoarthritis.

Résumé

Nous avons montré précédemment que l’inactivation du facteur de l’hypoxie 1-α (HIF-1α) dans les chondrocytes du cartilage de conjugaison inhibe très nettement la génération d’énergie anaérobie et la synthèse de la matrice. Utilisant l’immuno-histochimie nous avons analysé la distribution spatiale de HIF-1, et ses gène- cibles dans le cartilage normal et dans le cartilage d’articulations avec arthrose. Nous avons détecté des HIF-1α et ses gène-cibles dans les deux types de cartilage. Dans le cartilage arthrosique le nombre de chondrocytes marqués HIF-1α, Glut-1 et PGK-1 a augmenté avec la sévérité de l’arthrose. La synthèse de la matrice activée et le niveau d’oxygène fortement diminué sont des caractéristiques du cartilage arthrosique. Donc nous supposons que les chondrocytes dépendent de la fonction adaptative de HIF-1 pour maintenir le niveau d’ATP et de cette façon la synthèse de la matrice pendant l’évolution de l’arthrose.

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Acknowledgements

This work was supported in part by the Ministry of Research (IZKF-Erlangen, D5) and by a grant from the Deutsche Forschungsgemeinschaft (PF 383/4).

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Authors and Affiliations

  1. Division of Orthopaedic Rheumatology, Department of Orthopaedic Surgery im Waldkrankenhaus St. Marien, University of Erlangen-Nuremberg, Rathsbergerstr. 57, 91054, Erlangen, Germany

    David Pfander & Bernd Swoboda

  2. Department of Hepatology and Gastroenterology, Charité-Universitätsmedizin Berlin, Campus Virchow-Klinikum, Berlin, Germany

    Thorsten Cramer

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  1. David Pfander
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Correspondence to David Pfander.

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Pfander, D., Cramer, T. & Swoboda, B. Hypoxia and HIF-1α in osteoarthritis. International Orthopaedics (SICOT) 29, 6–9 (2005). https://doi.org/10.1007/s00264-004-0618-2

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  • DOI: https://doi.org/10.1007/s00264-004-0618-2

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