Effects of Sodium Hyaluronic Acid on Fibrinolytic Factors in Humans with Arthropathies

High molecular weight (90- to 100-kDa) plasminogen activator (PA) urokinase-type/inhibitor-1 ([u-PA/PAI-1] complex) and 55-kDa u-PA were identified in synovial fluid collected from 12 osteoarthritis (OA) patients given hyaluronic acid (HA) into the knee joint. HA administration led to an increase in levels of u-PA and PAI-1 antigen as well as increases in the u-PA:PAI-1 ratio. In inhibition of their symptoms, the fibrinolytic activity was progressively suppressed. The u-PA content was higher at the weight-bearing site in OA and rheumatoid arthritis (RA) patients compared to cartilage tissue from controls. The PAI-1 content was higher in osteophyte-forming sites and in RA, compared to controls. Weight-bearing sites in OA patients expressed a high u-PA mRNA level but a low PAI-1 mRNA level. Osteophyte-forming sites in OA patients expressed a low u-PA mRNA level but a high PAI-1 mRNA level. The levels of u-PA and PAI-1 antigen increased in cartilage tissues exposed to mechanical stress. In contrast, the release of u-PA and PAI-1 antigens from specimens was suppressed with HA. At the weight-bearing site, the levels of matrix metalloproteinase (MMP) were high and levels of TIMP (tissue inhibitor of metalloproteinase) mRNA expression were low. In osteophyte-formed sites, the levels of TIMP were high and the levels of MMP mRNA expression low. These findings suggest that regulation of fibrinolysis may play a important role in the matrix of articular cartilage with arthropathy.