Chondrocyte-mediated catabolism of aggrecan: evidence for a glycosylphosphatidylinositol-linked protein in the aggrecanase response to interleukin-1 or retinoic acid.
The control of chondrocyte-mediated degradation of aggrecan has been studied in rat chondrosarcoma cells and bovine cartilage explants treated with either IL-1 or retinoic acid. The capacity of glucosamine to inhibit the aggrecanase-mediated response (J. D. Sandy, D. Gamett, V. Thompson, and C. Verscharen (1998) Biochem. J. 335, 59-66) has been extended to an investigation of the effect of other hexosamines. Mannosamine inhibits the aggrecanase response to both IL-1 and RA at about one-tenth the concentration of glucosamine in both rat cell and bovine explant systems. This effect of mannosamine appears to be due to its capacity to inhibit the synthesis of glycosylphosphatidylinositol (GPI)-linked proteins by chondrocytes since the GPI synthesis inhibitor 2-deoxyfluoroglucose (2-DFG) also inhibited the aggrecanase response to IL-1b and RA in rat cells. Moreover, phosphatidylinositol-specific phospholipase C (PIPLC) treatment of rat cells markedly inhibited the aggrecanase response to IL-1b and RA. These inhibitory effects of mannosamine, 2-DFG, and PIPLC in rat cells did not appear to be due to an interference with general biosynthetic activity of the cells as measured by [3H]proline incorporation into secreted proteins. We suggest that the aggrecanase response by chondrocytes to IL-1 and RA is dependent on the activity of a GPI-anchored protein on the chondrocyte cell surface.
Biochemistry Section, Shriners Hospital, Tampa Unit, 12502 North Pine Drive, Tampa, Florida, 33612, USA. jsandy@shctampa.usf.edu
J D
JD
Sandy
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V
Thompson
C
C
Verscharen
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D
Gamett
D053674:Aggrecans; D000818:Animals; D002356:Cartilage / Q000378:metabolism; D002417:Cattle; D019902:Chondrocytes / Q000378:metabolism*; D046508:Culture Techniques; D003847:Deoxyglucose / Q000032:analysis / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D010450:Endopeptidases / Q000378:metabolism*; D016326:Extracellular Matrix Proteins; D017261:Glycosylphosphatidylinositols / Q000378:metabolism*; D006595:Hexosamines / Q000032:analysis / Q000494:pharmacology; D007375:Interleukin-1 / Q000494:pharmacology*; D037181:Lectins, C-Type; D043265:Phosphatidylinositol Diacylglycerol-Lyase; D054801:Phosphoinositide Phospholipase C; D011509:Proteoglycans / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051381:Rats; D014212:Tretinoin / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D010738:Type C Phospholipases / Q000032:analysis / Q000494:pharmacology
C508321:Acan protein, rat; D053674:Aggrecans; D016326:Extracellular Matrix Proteins; D017261:Glycosylphosphatidylinositols; D006595:Hexosamines; D007375:Interleukin-1; D037181:Lectins, C-Type; D011509:Proteoglycans; C008322:mannosamine; D014212:Tretinoin; D003847:Deoxyglucose; D010738:Type C Phospholipases; D054801:Phosphoinositide Phospholipase C; D010450:Endopeptidases; C083641:aggrecanase; D043265:Phosphatidylinositol Diacylglycerol-Lyase