Abstract
Our study aimed to investigate the role of an HMG-CoA reductase inhibitor (atorvastatin) in human osteoarthritic chondrocytes and to test the in vivo effects of intra-articular injections of atorvastatin in a rabbit experimental osteoarthritis model.
Human articular osteoarthritic chondrocytes were cultured in the presence and absence of atorvastatin. mRNA and protein expression of MMP-13, COL2A1 and aggrecan were measured using real-time PCR and Western Blot analysis.
New Zealand rabbits (n=15) underwent bilateral anterior cruciate ligament transection (ACLT) to induce osteoarthritic degeneration and received intra-articular injections of atorvastatin and normal saline in the left and right knees respectively. The first injection was at the time of ACLT and injections were repeated every 3 days for 3 weeks. Data were obtained from macroscopic and histological evaluation as well as from gene expression analysis for COL2A1, aggrecan and MMP-13.
Incubation of the cultures with atorvastatin produced a decreasing effect in MMP-13 expression. Regarding aggrecan and COL2A1 expression a significant increase was observed.
Gross morphologic evaluation showed that the joints which received atorvastatin injections, showed minimal cartilage erosion, compared to the non-treated knees where the cartilage was markedly eroded, especially on the medial knee compartment. These results were supported by histological and gene expression analysis. The mRNA expression of MMP-13 was significantly reduced in the cartilage of the statin-treated knee joints, while the expression of COL2A1 and aggrecan was increased.
The clinical relevance of our results indicates a potential protective effect of atorvastatin on articular cartilage undergoing osteoarthritic degeneration.
Correspondence should be addressed to Anastasia C. Tilentzoglou MD, General Secretary of the Board of Directors of HAOST, 20 A. Fleming Str. (N.Filothei), Gr. 15123 Maroussi, Athens Greece. E-mail: info@eexot.gr
