The Detection Of Urokinase Type Plasminogen Activator(uPA) And Matrix Metalloproteinase-3 (MMP-3) In Serum And Synovial Fluid Of Rabbit With Osteoarthritis And Its Significance

Purpose:To investigate the effects of the urokinase type plasminogen activator in the pathogenesis of osteoarthritis by study on the histological change of cartilage,synovium of knee joint and the induction of cytokines in synovial fluid in experimental animals with intra-articular injection of urokinase type plasminogen activator into the one knee joint of rabbits. Methods:The 66 rabbits were divided into experimental animals and control animals according to the weight and the sex, 24 cases for experimental group and 48 cases for control group. Experimental animals were randomly divided into three groups acording to time, 8 cases for each group and were injected intraarticularly with 0.4ug/0.2ml uPA. Control animals were randomly divided into seven groups, 6 cases for each group, included one blank control group which was not given any injection medicine; three negative control groups were injected intraarticularly with 0.2ml normal saline; three positive control groups were transected of the medial collateral ligament, medial meniscectomy, anterior cruciate ligament and posterior cruciate ligament. The rabbits were respectively sacrificed at weeks 4, 8, and 12 week. Histological change of cartilage and synovium of knee joint and the induction of cytokines in synovial fluid in each animals were detected.Results:1. Histological detection and scale of rabbit right kneel articular cartilage in experimental groups under light microscope: the surface of the joint cartilage showed defects, damages, structural breakage, and the number of cartilage cell decreased. Collagen fiber hyperplasia and tidal line of complete break while 4-layer structure of articular cartilage in the blank control group and negative control groups was clear to see, and cartilage cells were arranged in order with complete tidal line. Mankin's evaluation of the degeneration in articular cartilage in experimental groups and negative control groups: the scores at 4^th ,8^th ,12^th weeks were higher in experimental groups than those in the negative control groups(P<0.01). 2. The uPA induced OA model was similar with Hulth-OA model in histology of cartilage and imageological findings of knee.3. Imageological findings comformed to OA of human-being,the uPA,MMP-3 contents in the synovial fluid were markedly higher than that of in the negative control groups. There is a significant linear relationship between uPA and MMP-3 in serum and synovial fluid from the experimental groups(P<0.01), and the contents increased to different extents with increase of cartilage degeneration.Conclusion:1. Experimental knee OA of rabbits with intra-articular injection uPA is in conformity with the appearance of OA in histomorphology and pathematology, and production process is simple, therefore it is a good animal model of experimental OA.2. As one of catabolic enzymes that act on the degradation of extracellular matrix, uPA not only directly degenerates cartilage, but activates other catabolic enzymes of extracellular matrix and correlated cytokines. It maybe plays a key role during the occurrence and development of of OA as one of inducing factor.3. The MMP-3 and uPA levels in serum and synovial fluid of the knees can reflect the degree of synovitis and accumulative cartilage injury as a biomarker, especially accumulative cartilage injury.