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Matrix metalloproteinase expression levels suggest distinct enzyme roles during lumbar disc herniation and degeneration

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Abstract

The disruption of the extracellular disc matrix is a major hallmark of disc degeneration. This has previously been shown to be associated with an up-regulation of major matrix metalloproteinase (MMP) expression and activity. However, until now hardly any data are available for MMP/TIMP regulation and thereby no concept exists as to which MMP/TIMP plays a major role in disc degeneration. The objective of this study was, therefore, to identify and quantify the putative up-regulation of MMPs/TIMPs on the mRNA and protein level and their activity in disc material in relation to clinical data and histological evidence for disc degeneration. A quantitative molecular analysis of the mRNA expression levels for the MMPs (MMPs-1, -2, -3, -7, -8, -9, -13) and the MMP inhibitors (TIMPs-1 and -2) was performed on 37 disc specimens obtained from symptomatic disc herniation or degeneration. In addition, disc specimens from patients without disc degeneration/herniation (=controls) were analyzed. Expression of MMPs-1, -2, -3, -7, -8, -9, -13 and TIMPs-1, -2 was analyzed using quantitative RT-PCR, normalized to the expression level of a house keeping gene (GAPDH). Gene expression patterns were correlated with MMP activity (in situ zymography), protein expression patterns (immunohistochemistry), degeneration score (routine histology) and clinical data. MMP-3 mRNA levels were consistently and substantially up-regulated in samples with histological evidence for disc degeneration. A similar but less pronounced up-regulation was observed for MMP-8. This up-regulation was paralleled by the expression of TIMP-1 and to a lesser extent TIMP-2. In general, these findings could be confirmed with regard to protein expression and enzyme activity. This study provides data on the gene and protein level, which highlights the key role of MMP-3 in the degenerative cascade leading to symptomatic disc degeneration and herniation. Control of the proteolytic activity of MMP-3 may, therefore, come into the focus when aiming to develop new treatment options for early disc degeneration.

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Acknowledgments

This study was supported by a grant from the SynOs Stiftung für Orthopädische Chirurgie, Münsingen, Switzerland (Grant no. 1028-01) and the AOSPINE Switzerland SRN 02/103 and AOSBRC-07-03.

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Authors and Affiliations

  1. Department of Clinical Chemistry and Clinical Biochemistry, Ludwig-Maximilians-University München, Munich, Germany

    Beatrice E. Bachmeier

  2. Institute of Pathology, Academic Hospital München-Bogenhausen, Munich, Germany

    Andreas Nerlich

  3. Department of Neurosurgery, Academic Hospital München-Bogenhausen, Munich, Germany

    Norbert Mittermaier & Christianto Lumenta

  4. Department of Pathology, Ludwig-Maximilians-University München, Munich, Germany

    Christoph Weiler

  5. Spine Research Group, Competence Centre for Applied Biotechnology and Molecular Medicine, University of Zurich, Zurich, Switzerland

    Karin Wuertz & Norbert Boos

  6. Centre for Spinal Surgery, University of Zurich, University Hospital Balgrist, Forchstrasse 340, 8008, Zurich, Switzerland

    Norbert Boos

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  1. Beatrice E. Bachmeier
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Correspondence to Norbert Boos.

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Bachmeier, B.E., Nerlich, A., Mittermaier, N. et al. Matrix metalloproteinase expression levels suggest distinct enzyme roles during lumbar disc herniation and degeneration. Eur Spine J 18, 1573–1586 (2009). https://doi.org/10.1007/s00586-009-1031-8

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  • DOI: https://doi.org/10.1007/s00586-009-1031-8

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