Increased stromelysin-1 (MMP-3), proteoglycan degradation (3B3-and 7D4) and collagen damage in cyclically load-injured articular cartilage

Objective: To determine whether load-induced injury causes alterations in proteoglycan (PG), stromelysin-1 (MMP-3) and collagen in articular cartilage. Methods: Mature bovine cartilage was cyclically loaded at 0.5 Hz with 1 and 5 MPa for 1, 6 and 24 h. Immediately after loading explants were evaluated for cell viability. Alterations in matrix integrity were determined by measuring PG content, PG degradation using 7D4 and 3B3(-) antibodies, broken collagen using COL2-3/4m antibody, and stromelysin-1 content using a MMP-3 antibody. Results: Mechanical load caused cell death and PG loss starting from the articular surface and increasing in depth with loading time. There was a decrease in the 7D4 epitope (native chondroitin sulfate) in the superficial zone of cartilage loaded for longer than 1 h, but an increase around chondrocytes in the deep zone. The 3B3(-) staining for degraded/abnormal chondroitin-4-sulfate neoepitope appeared only in cartilage loaded under the most severe condition (5 MPa, 24 h). The elevation of stromelysin-1 was co-localized with broken collagen (COL2-3/4m) at the articular surface in explants loaded with 1 and 5 MPa for 24 h. Conclusions: Cell death and PG loss occurred within 6 h of cyclic loading. The elevation of MMP-3 following cell death was consistently found in the superficial zone of loaded cartilage. Since MMP-3 can degrade PG and super-activate procollagenase, the increase of MMP-3 can therefore induce matrix degradation and PG depletion in mechanically injured articular cartilage, both of which are important to the development of osteoarthritis. (C) 2004 OsteoArthritis Research Society International. Published by Elsevier Ltd. All rights reserved.