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 proteolytic enzymes plays a critical role in cartilage degradation during osteoarthritis. Urokinase receptor (uPAR), a glycosyl-phosphatidylinositol-linked glycoprotein present on the cell surface of various cell types such as cancer cells, fibroblasts, synoviocytes, and chondrocytes, is a key regulator of the plasmin-mediated pericellular proteolysis. Recently, in arthritic synovial tissue increased uPAR expression has been detected. By immunohistochemical analysis we observed, in addition, enhanced expression of uPAR in chondrocytes 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-integrin, as demonstrated by double immunostaining with specific antibodies. Furthermore, uPAR was present in caveolae-like structures of chondrocytes as detected by immunoelectron microscopy. Finally, both caveolin and beta 1-integrin were coprecipitated with uPAR-specific antibodies from cell extracts suggesting that these proteins may form functional complexes in human chondrocytes. The localization of uPAR in caveolae and its close association with caveolin and beta 1-integrin points to a significance of uPAR-mediated signaling pathways in human chondrocytes.
Schwab
W
W
Institute of Anatomy, Technical University Dresden, Medical Faculty Carl Gustav Carus, Fiedlerstrasse 42, 01307 Dresden, Germany. Wolfgang.Schwab@mailbox.tu-dresden.de
Gavlik
J M
JM
Beichler
T
T
Funk
R H
RH
Albrecht
S
S
Magdolen
V
V
Luther
T
T
Kasper
M
M
Shakibaei
M
M
D002358:Cartilage, Articular / Q000166:cytology / Q000378:metabolism*; D051242:Caveolin 1; D022461:Caveolins / Q000378:metabolism*; D002478:Cells, Cultured; D019902:Chondrocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D019012:Integrin beta1 / Q000378:metabolism*; D007719:Knee Joint / Q000166:cytology; D010003:Osteoarthritis / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000378:metabolism*; D055293:Receptors, Urokinase Plasminogen Activator; D013755:Tetradecanoylphorbol Acetate / Q000031:analogs & derivatives* / Q000494:pharmacology
C495540:CAV1 protein, human; D051242:Caveolin 1; D022461:Caveolins; D019012:Integrin beta1; C524898:PLAUR protein, human; D011956:Receptors, Cell Surface; D055293:Receptors, Urokinase Plasminogen Activator; C016658:phorbolol myristate acetate; D013755:Tetradecanoylphorbol Acetate