Protective effect of atorvastatin in cultured osteoarthritic chondrocytes.
The aim of our study was to evaluate the in vitro effect of an HMG-CoA reductase inhibitor, atorvastatin, on the expression of significant anabolic and catabolic genes in human osteoarthritic chondrocytes and to explore the metabolic pathways involved in this process. Human articular osteoarthritic chondrocytes were cultured in the presence and absence of atorvastatin (10 and 50 micromol/L) for 24 h. Metalloproteinase 13 (MMP-13), collagen type II (COL2A1), and aggrecan (AGC) mRNA expression levels were evaluated by real-time PCR, and protein expression levels by Western blot analysis. IL-1beta levels in culture medium was analyzed with ELISA. The effect of the treatment with the mevalonate isoprenoid derivatives farnesol and geranylgeraniol, or the cholesterol precursor squalene, was evaluated in the atorvastatin osteoarthritic chondrocyte cultures. Incubation of osteoarthritic chondrocyte cultures with atorvastatin produced a significant dose-dependent reduction in IL-1beta production. Atorvastatin supplementation in cultures produced a decrease in MMP-13 mRNA and protein expression levels, which was reversed by the addition of farnesol. Regarding AGC and COL2A1 mRNA expression, a significant increase was observed only in chondrocytes cultures treated with 50 micromol/L atorvastatin. Our findings suggest that atorvastatin may have potential chondroprotective effects mostly by reducing cartilage degradation.
Simopoulou
Theodora
T
Laboratory of Cytogenetics and Molecular Genetics, University of Thessaly Medical School, Larissa, Greece.
Malizos
Konstantinos N
KN
Poultsides
Lazaros
L
Tsezou
Aspasia
A
D000368:Aged; D000369:Aged, 80 and over; D053674:Aggrecans / Q000187:drug effects / Q000378:metabolism; D000069059:Atorvastatin; D002358:Cartilage, Articular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D002478:Cells, Cultured / Q000187:drug effects* / Q000378:metabolism; D019902:Chondrocytes / Q000187:drug effects* / Q000378:metabolism; D024043:Collagen Type II / Q000187:drug effects / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005260:Female; D006538:Heptanoic Acids / Q000008:administration & dosage*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage*; D053583:Interleukin-1beta / Q000187:drug effects / Q000378:metabolism; D007719:Knee Joint / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D008297:Male; D053509:Matrix Metalloproteinase 13 / Q000187:drug effects / Q000378:metabolism; D008875:Middle Aged; D020370:Osteoarthritis, Knee / Q000517:prevention & control*; D011758:Pyrroles / Q000008:administration & dosage*
D053674:Aggrecans; D024043:Collagen Type II; D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D053583:Interleukin-1beta; D011758:Pyrroles; D000069059:Atorvastatin; D053509:Matrix Metalloproteinase 13