A correlation between knee cartilage degradation observed by arthroscopy and synovial proteinases activities

Abstract

Objective: A novel study has been carried out to characterize the amount and activity levels of metalloproteinases (i.e., MMP-1, MMP-2, MMP-3, MMP-8, MMP-9 and MMP-13) and of their inhibitors (i.e., TIMP-1 and TIMP-2) in synovial fluid from patients (n ϭ 56) with different degrees of either chondral lesions or knee arthritis identified and classified by arthroscopy. Design and methods: Zymographies, Western blotting and ELISA tests have been used to correlate the disease stage, as determined by arthroscopy, and both the amount and the activation state of different MMPs and of their inhibitors. Results: Analysis of data obtained demonstrates that the degree of cartilage degradation, as seen by arthroscopy, is strictly related to the activity of some synovial MMPs, in particular MMP-2 and MMP-13 and on reduced inhibitory effect of MMP-2 by TIMP-2; in addition, a serine protease weighing about 125 kDa appears only in patients with severe cartilage degradation, i.e., with knee arthritis. Conclusions: On the whole, this is the first study in which an analysis of synovial MMPs/other proteinases activity and TIMPs has been strictly related to arthroscopy results in patients with different degrees of osteoarthritis. Results indicate that an imbalance between specific MMP activities and the amount of TIMPs and of its inhibitory efficiency is crucial for the disease evolution and it is related to the disease stage.

Temporospatial expression of matrix metalloproteinases and tissue inhibitors of matrix metalloproteinases in mouse antigen-induced arthritis

“…e and k are staining controls incubated without the primary antibody. The bar in b corresponds to 1,000 lm in a, f and to 120 lm in other panels vium (Reboul et al 1996), and the amount and activity of MMP-13 in synovial fluid has been found to directly correlate with advanced stages of cartilage lesions in the knee joint (Schmidt-Rohlfing et al 2002;Marini et al 2003). Our recent findings that adenovirus-mediated overexpression of MMP-13 in synovium induces inflammatory arthritis in mouse also support the role of MMP-13 in synovial inflammation (Joronen et al 2004).…”

Therapeutic Effect of Siegesbeckia pubescens on Cartilage Protection in a Rabbit Collagenase-Induced Model of Osteoarthritis

“…Dual deletion of ADAMTS-4 and ADAMTS-5 in mice resulted in significant protection against proteoglycan degradation, which was comparable with that observed with deletion of ADAMTS-5 alone, and decreased the severity of murine OA (40). Recent studies show that collagen and proteoglycan release from cartilage can indeed be prevented by treatment with an inhibitor of MMP transcription (41,42). It has been also reported that increased levels of MMP-3 are co-localized with cell death and broken cartilage (proteoglycan and collagen) in models of OA (43 -45).…”

Association between the abnormal expression of matrix‐degrading enzymes by human osteoarthritic chondrocytes and demethylation of specific CpG sites in the promoter regions

“…One source of these proteinases may be the synovium, with the presumption that the enzymes diffuse into the cartilage matrix. Some MMPs tend to be elevated in the synovial fluid of OA patients (11,12), although not as much as in the inflammatory synovium of rheumatoid arthritis patients (11). The second most important source of degradative enzymes is the chondrocytes of OA cartilage (13,14).…”