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Published in: European Spine Journal 11/2009

01-11-2009 | Original Article

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

Authors: Beatrice E. Bachmeier, Andreas Nerlich, Norbert Mittermaier, Christoph Weiler, Christianto Lumenta, Karin Wuertz, Norbert Boos

Published in: European Spine Journal | Issue 11/2009

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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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Metadata
Title
Matrix metalloproteinase expression levels suggest distinct enzyme roles during lumbar disc herniation and degeneration
Authors
Beatrice E. Bachmeier
Andreas Nerlich
Norbert Mittermaier
Christoph Weiler
Christianto Lumenta
Karin Wuertz
Norbert Boos
Publication date
01-11-2009
Publisher
Springer-Verlag
Published in
European Spine Journal / Issue 11/2009
Print ISSN: 0940-6719
Electronic ISSN: 1432-0932
DOI
https://doi.org/10.1007/s00586-009-1031-8

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