Stromelysin, tissue inhibitor of metalloproteinases and proteoglycan fragments in human knee joint fluid after injury

Objective. To determine in a cross sectional study the concentrations of stromelysin, tissue inhibitor of metalloproteinases (TIMP), and proteoglycan fragments in knee synovial fluid (SF) at different times after injury to cruciate ligament or meniscus. Methods. Joint fluid samples were obtained from patients with knee injury diagnosed by arthroscopy. Concentrations of stromelysin-1 and TIMP-1 were determined by immunoassay with monoclonal and polyclonal antibodies. Cartilage proteoglycan fragments were quantified by immunoassay with polyclonal antibodies or by dye precipitation. Results. Average concentrations of stromelysin increased 40-fold in association with injury, and after about 6 months decreased to a plateau level about 10-fold increased compared to a reference group with healthy knees. TIMP and proteoglycan levels also increased in similar temporal patterns, but less markedly. Increased average SF levels of these markers were maintained for at least 17 years after injury. SF from knees with injury contained a 1.5 to 2.5 molar excess of stromelysin over TIMP, while reference joint fluids contained a 2-fold molar excess of TIMP over stromelysin. Conclusion. The persistent changes in SF markers after joint injury may be associated with the cartilage destruction and frequent development of posttraumatic osteoarthritis in this group of patients