TY - JOUR
T1 - Expression of the urokinase-type plasminogen activator receptor in human articular chondrocytes
T2 - Association with caveolin and β1-integrin
AU - Schwab, W.
AU - Gavlik, J. M.
AU - Beichler, T.
AU - Funk, R. H.W.
AU - Albrecht, S.
AU - Magdolen, V.
AU - Luther, T.
AU - Kasper, M.
AU - Shakibaei, M.
N1 - Funding Information:
Acknowledgements The authors thank Mrs. B. Georgiewa, Mrs. C. Nipproschke, and Mrs. K. Pehlke for the execution of the immunohistochemical preparations and cell culture studies. Mr. Philippe de Souza’s and Mrs. Angelika Steuer’s technical assistance are gratefully acknowledged. This work was supported by the Deutsche Forschungsgemeinschaft (DFG, Wo 494/9–1-479/98; DFG grant Sh 48/2–2, Sh 48/2–3).
PY - 2001
Y1 - 2001
N2 - 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 β1-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 β1-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 β1-integrin points to a significance of uPAR-mediated signaling pathways in human chondrocytes.
AB - 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 β1-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 β1-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 β1-integrin points to a significance of uPAR-mediated signaling pathways in human chondrocytes.
KW - Arthritis
KW - Cartilage
KW - Caveolin
KW - Integrin
KW - uPAR
UR - http://www.scopus.com/inward/record.url?scp=0035052269&partnerID=8YFLogxK
U2 - 10.1007/s004180100255
DO - 10.1007/s004180100255
M3 - Article
C2 - 11405060
AN - SCOPUS:0035052269
SN - 0948-6143
VL - 115
SP - 317
EP - 323
JO - Histochemistry and Cell Biology
JF - Histochemistry and Cell Biology
IS - 4
ER -
