Pravastatin suppresses matrix metalloproteinase expression and activity in human articular chondrocytes stimulated by interleukin-1β.
BACKGROUND
Matrix metalloproteinases are catabolic enzymes that play a key role in the articular cartilage degeneration evident in degenerative and inflammatory conditions of articular cartilage. The aim of this study is to assess the ability of pravastatin to modify matrix metalloproteinase (MMP) messenger RNA (mRNA) expression and enzyme activity in a culture of normal human chondrocytes stimulated by interleukin-1β.


METHODS
Normal human chondrocytes were stimulated with interleukin (IL)-1β for 6 h to induce MMP expression, simulating a catabolic state, and then treated with pravastatin (1, 5 and 10 μM) for a further 18 h before cell lysates and supernatants were harvested. Cells stimulated with IL-1β but not treated with pravastatin served as controls. Real-time polymerase chain reaction (PCR) was used to assess expression of MMP-3 and MMP-9 mRNA. MMP enzyme activity was assessed using a fluorescent MMP-specific substrate. Statistical analysis was performed using analysis of variance (ANOVA).


RESULTS
MMP-3 and MMP-9 mRNA expression was reduced at all concentrations tested with statistically significant trends in reduction (p = 0.002 and <0.001, respectively). Analysis 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).


CONCLUSIONS
Treatment with pravastatin of stimulated human chondrocytes leads to significant down-regulation of selected MMP genes and a non-significant reduction in MMP enzyme activity. Our results provide further evidence that statins may have a role to play in future treatment of disease affecting articular chondrocytes.
School of Medicine and Medical Sciences, University College Dublin, Dublin, Ireland. joseph.f.baker@gmail.com
Joseph F
JF
Baker
Pauline M
PM
Walsh
Damien P
DP
Byrne
Kevin J
KJ
Mulhall
D015153:Blotting, Western; D002358:Cartilage, Articular / Q000166:cytology / Q000201:enzymology*; D002478:Cells, Cultured; D019902:Chondrocytes / Q000166:cytology / Q000201:enzymology*; D015536:Down-Regulation / Q000187:drug effects*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology; D053583:Interleukin-1beta / Q000494:pharmacology*; D020782:Matrix Metalloproteinases / Q000096:biosynthesis / Q000235:genetics*; D017035:Pravastatin / Q000494:pharmacology*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction
D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D053583:Interleukin-1beta; D012333:RNA, Messenger; D020782:Matrix Metalloproteinases; D017035:Pravastatin