Abstract
Introduction
Matrix metalloproteinases (MMP) play a key role in cartilage degradation in osteoarthritis. Statins are a potential suppressor of MMPs. The aim of this research was to assess the efficacy of Pravastatin in suppressing MMP gene and protein expression in an in vitro model.
Methods
We stimulated normal human chondrocytes with IL-1b for 6 hours to induce MMP expression and then treated with Pravastatin (1, 5 & 10 mM) for a further 18 hours. Cells stimulated with IL-1b but not treated with Pravastatin served as controls. Real-time PCR was used to assess expression of MMP-3 and MMP-9 mRNA. MMP enzyme activity was assessed using a fluorescent MMP-specific substrate. Staistical analysis was performed using ANOVA.
Results
MMP-3 and -9 mRNA expression was reduced at all concentrations tested with a statistically significant trends in reduction (p=0.002 and < 0.001 respectively). Analaysis of culture supernatants revealed that Pravastatin treatment led to a reduction in total MMP activity but not to a statistically significant degree (p=0.07).
Conclusion
We conclude that treatment with Pravastatin of stimulated human chondrocytes leads to a down regulation of selected MMP genes and a reduction in MMP enzyme activity. Our results are further evidence that statins may have a role to play in the treatment of osteoarthritis and other disorders of cartilage degradation.
