Chondroprotective effect of simvastatin in an experimental osteoarthritis model via inhibition of matrixmetalloproteinase

Objective: To investigate the chondroprotective effect of orally adminstrated simvastatin via the inhibition of matrixmetalloproteinase-3 (MMP-3) enzyme in an experimental model of knee osteoarthritis (OA).Materials and Methods:In this study 27 Wistar Albino rats weighing 250-300 gr were used. Animals were divided into 3 Groups. Animals comprising Group 1 and Group 2 underwent a anterior cruciate ligament transection via using a medial arthrotomy to simulate a knee instability altering articular cartilage loading that leads to mechanicaly induced osteoarthritis (OA). After the surgical procedure each animal in Group 2 was treated with oraly adminstrated Simvastatin (Merck Sharp & Dohme, Middlesex,U.K) 20/mg/kg/day for 6 weeks. In Group 3 knees of healthy animals were taken as controls. 9 knee joints in all groups were subseqeuntly diveded into femur (F) and tibia (T) subgroups. All animals were housed in different cages according to their groups and were allowed unlimited activity. All animals were sacrificed 6 weeks after the operation by using an intravenous overdose anesthesia and the knee joints were assesed by histopathological and immunohistochemical methods.Histopathological assesment was made by using the OARSI (Ostearthritis Research Society İnternational) cartilage OA pathology assesment system based on 6 grades and 4 stages reflecting extent of OA over the joint surface.Immunohistochemical asessment was made by identifying the percentage of MMP-3 stained condrocytes in the articular cartilage of femur and tibia respectively.Results: 9 knees of 9 animals were included in each study group. Histopathological examination showed that Group 1 (ACLT) and Group 2 (ACLT +simvastatin) had statistically significant higher OARSİ cartilage OA pathology assesment scores compared with the untreated control knees. However animals in Group 2 treated with simvastatin had statistically lower scores compared to those of Group 1, revealing a decrease in OA progression.The percentage of matrixmetalloproteinase staining between Group 2 (ACLT+simvastatin) and Group 1 (ACLT) showed statistacally significant difference, whereas there was no difference between Group 2 and Group 3 (control ).Conclusion: Orally administrated Simvastatin had benefical effects on progression of osteoarthritis in an experimental animal model of osteoarthritis achieved by transecting the anterior crutiate ligament. Simvastatin may be used as a disease modifying drug in the inflammatory phase of the disease achieving chondroprotective effect on knee joint cartilage and has a promising role in prevention of osteoarthritis in the future.