Abstracts Posters SICOT-SOF meeting Gothenburg 2010 _2_

Poster
Topic: General Orthopaedics
Abstract number: 26467
PRAVASTATIN REDUCES MMP-3 AND MMP-9 GENE EXPRESSION IN
INTERLEUKIN-1-β STIMULATED NORMAL HUMAN CHONDROCYTES
Joseph BAKER 1 , Walsh PAULINE 1 , Kevin MULHALL 2
1 University College Dublin, Dublin (IRELAND), 2 Mater Misericordiae University
Hospital, Dublin (IRELAND)
Introduction: Pharmacological agents for the treatment of osteoarthritis (OA) only
control symptoms. With the increasing burden of this disease worldwide,
development of a disease-modifying drug is crucial. Statins, with well-reported antiinflammatory
properties, are one such potential agent. We aimed to investigate the
efficacy of Pravastatin to modify the gene expression of three selected matrix
metalloproteinases (MMPs). Methods: Normal human chondrocytes were grown
under standard laboratory conditions. After stimulation with interleukin-1- (IL-1-) to
simulate OA for 6-hours they were treated with Pravastatin at 1, 5, 10 and 50M for a
further 18-hours. IL-1- stimulated cells without treatment with Pravastatin were used
as a control. PCR was used to measure change in gene expression of MMP-3, MMP-
9 and MMP-13 all enzymes contributing to articular cartilage destruction. Results: At
the 10 and 50M concentrations, there was statistically significant reduction in
expression of MMP3 (p=0.036, 0.006 respectively, one sample t-test). There was a
non-significant trend toward down-regulation of MMP-9 mRNA expression with
increasing concentration (all p>0.05). There was no obvious trend, nor statistically
significant down-regulation of MMP-13 gene expression at any dose. Conclusion:
Pravastatin shows some promise for the treatment of OA with the ability to downregulate
mRNA expression of MMP-3 and MMP-9. Further work is warranted in this
field to confirm that gene expression changes correlate with reduced enzyme activity
and reduced articular cartilage degradation.
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