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Expression of glucose transporters GLUT-1, GLUT-3, GLUT-9 and HIF-1α in normal and degenerate human intervertebral disc

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Abstract

The glucose transporters GLUT-1 and GLUT-3 are targets of the hypoxia-inducible transcription factor HIF-1α and it has been shown that nucleus pulposus (NP) cells in rat intervertebral discs (IVD) express both HIF-1α and GLUT-1. However, there is limited data on the expression of HIF-1α and GLUTs in human IVD. The aim here was to (1) determine whether, like articular chondrocytes, human IVD cells express GLUT-1, 3 and 9 and whether there was any co-expression with HIF-1α; and (2) to localise expression of the GLUT isoforms in the disc and identify any changes during degeneration. Real-time PCR was used to identify expression of GLUT1, 3, 9 and HIF-1α mRNAs and immunohistochemistry was used to analyse protein expression and localisation of GLUTs in normal and degenerate IVD biopsies. Results confirmed HIF-1α, GLUT1, 3 and 9 mRNA expression in NP and AF and co-expression of each GLUT isoform with HIF-1α in the NP, but not the AF. Immunohistochemistry demonstrated regional differences in GLUT expression, with the highest expression being in the NP. GLUT expression also changed as degeneration progressed. This study demonstrates that NP and AF cells have different GLUT expression profiles that suggest regional differences in the metabolic nature of the human IVD and that this environment changes during degeneration.

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Acknowledgments

We would like to thank Dr. Stephen Baldwin (Faculty of Biological Sciences, University of Leeds) and Dr. Kelle Moley (Washington University School of Medicine, St Louis, MO, USA) for polyclonal antibodies to GLUT-1 and GLUT-9, respectively. We thank Dr. Christopher A. Moskaluk (Departments of Pathology, Biochemistry, and Molecular Genetics, University of Virginia Health System, Charlottesville, VA, USA) and the staff of the Cooperative Human Tissue Network of the National Cancer Institute (National Institutes of Health, Bethesda, MD, USA) for access to CHTN tissue microarrays. Thanks also to Dr. Christine Le Maitre for assistance with the real-time PCR. We gratefully acknowledge the support of the joint UK Research Councils’ Interdisciplinary Research Collaboration in Tissue Engineering (Biotechnology and Biological Sciences Research Council, Engineering and Physical Sciences Research Council, and Medical Research Council).

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None of the authors declare any conflicts of interest for this work.

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Authors and Affiliations

  1. Tissue Injury and Repair Group, Clinical and Laboratory Sciences, Faculty of Medical and Human Sciences, The University of Manchester, Manchester, M13 9PT, UK

    S. M. Richardson, R. Knowles, J. Tyler & J. A. Hoyland

  2. Division of Veterinary Medicine, School of Veterinary Medicine and Science, University of Nottingham, Sutton Bonington Campus, College Road, Sutton Bonington, Leicestershire, LE12 5RD, UK

    A. Mobasheri

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  1. S. M. Richardson
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Correspondence to J. A. Hoyland.

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Richardson, S.M., Knowles, R., Tyler, J. et al. Expression of glucose transporters GLUT-1, GLUT-3, GLUT-9 and HIF-1α in normal and degenerate human intervertebral disc. Histochem Cell Biol 129, 503–511 (2008). https://doi.org/10.1007/s00418-007-0372-9

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