| Osteoarthritis(OA) is a degenerative joint disease that affects a large and growing population, which characterized as cartilage degradation, scleroisis of subchondral bone and osteophyte formation. The progressive cartilage destruction that occurs in OA is thought to result from the proteolytic activity of matrix degrading enzymes such as matrix metalloproteinases (MMPs), and the inhibition of MMPs is effective in blocking the cartilage damage.To study the inhibitory activities and related mechanism of pyrogallic acid and myricetin to MMPs by fluorescent assays in vitro, and characterize the effects of MMP inhibitors on cartilage injury in rabbit osteoarthritis.We used DQ-gelatin as substrate to study the inhibitory activities of pyrogallic acid and myricetin to MMPs by fluorescent assays in vitro. The MMP inhibitions for these drugs were competitive revealed by enzyme kinetics analysis. Then we use an ophthalmologyical surgical scissors and cut off the back and front cross-ligamentum, the inside sub-ligamentum, the complete inside menisci to form an OA model in rabbit. After three weeks from surgery, we divided these 24 animals (female and male be in half) into three groups randomly (without conscious choice). The rabbits were injected with the physically salt water or 50mg/kg/day myricetin or pyrogallic acid into the knees for 14 days, and then sacrificed the next day. Cartilage tissues were evaluated with a histological scoring system.Pyrogallic acid and myricetin both can inhibit the enzymatic activities of MMPs, which was competitive revealed by enzyme kinetics analysis. There were obvious difference in the living conditions among the groups with or without drugs, and also we observed remarkable improvement in groups with drugs. These results demonstrated that MMP inhibition is effective in reducing the joint damage that occurs in the rabbit osteoarthritis model and support a potential therapeutic role for MMP inhibition in the treatment of OA. |
PDF Full Text Request