Expression of the urokinase-type plasminogen activator receptor in human articular chondrocytes: association with caveolin and beta(1)-integrin

The urokinase-type plasminogen activator (uPA) in concert with other proteo lytic enzymes plays a critical role in cartilage degradation during osteoar thritis. Urokinase receptor (uPAR), a glycosyl-phosphatidylinositol-linked glycoprotein present on the cell surface of various cell types such as canc er cells, fibroblasts, synoviocytes, and chondrocytes, is a key regulator o f the plasmin-mediated pericellular proteolysis. Recently, in arthritic syn ovial tissue increased uPAR expression has been detected. By immunohistoche mical analysis we observed, in addition, enhanced expression of uPAR in cho ndrocytes of arthritic samples of human cartilage compared to non-arthritic controls. Using in vitro cultured human chondrocytes, we analyzed whether uPAR is associated with structural proteins, which are known to be involved in cell signaling and activation, uPAR in phorbol-12-myristate-13-acetate- stimulated chondrocytes colocalized with caveolin as well as beta (1)-integ rin, as demonstrated by double immunostaining with specific antibodies. Fur thermore, uPAR was present in caveolae-like structures of chondrocytes as d etected by immunoelectron microscopy. Finally, both caveolin and beta (1)-i ntegrin were coprecipitated with uPAR-specific antibodies from cell extract s suggesting that these proteins may form functional complexes in human cho ndrocytes. The localization of uPAR in caveolae and its close association w ith caveolin and beta (1)-integrin points to a significance of uPAR-mediate d signaling pathways in human chondrocytes.