The effect of aggrecanases on advancement process of osteoarthritis in rat KNEE joint model

AIM:In this study, we aimed to evaluate the immunohistochemical expression of ADAMTS-4 and ADAMTS-5 in cartilage, synovium and synovial fibroblasts at different stages of MIA induced osteoarthritis (OA) model in rat knee joint. MATERIALS AND METHODS: A chemical model was induced by injecting 4 mg MIA to each knee joint of Wistar rats. Knee joints from rats sacrificed on day 5 (n = 10), 2nd week (n = 10), 4th week (n = 10), 8th week (n = 9) and 10th week (n = 6) were collected and frontal and sagittal sections are performed. Microscopic findings in HE and Toluidine blue stained preparations were evaluated according to Mankin and OARSI/ OOCHAS scores as well as a new scoring system that we developed. ADAMTS-4 and ADAMTS-5 expressions in cartilage, synovium and synovial fibroblasts were evaluated as percentage in the areas of the most intense staining and the data obtained were compared with other stages, and correlated with the Mankin, OARSI scores and synovitis score. RESULTS:No obvious cartilage pathology was detected in the 5th day, signs of cartilage degeneration were obvious at the 2nd week till end-stage OA findings were observed in the 8th and 10th weeks. ADAMTS-4 expression was significantly increased in the 2nd week, immunopositivity was detected in the superficial and middle zones of the cartilage. In the late stages, ADAMTS-4 immunexpression tended to increase again and full-thickness expression in the cartilage was observed. ADAMTS-5 expression increased significantly with the progression of cartilage lesion severity in the last stages and showed strong correlation with Mankin and OARSI scores. Strong expression for both ADAMTS-4 and ADAMTS-5 was observed at all stages in synovium and fibroblasts. CONCLUSIONS: Our findings suggest that ADAMTS-4 is effective both in the early and late stages of OA and ADAMTS-5 is effective in the late stage when lesions are exacerbated. Both enzymes are important in the pathogenesis of OA. Stronger and widespread immunexpression of both enzymes in synovium and fibroblasts, compared to cartilage, suggests that synovium plays an important role in the development of OA by producing aggrecanases.