MOLYBDATE IMPAIRS GLYCOSAMINOGLYCAN SULFATION IN RAT CARTILAGE

The mechanism by which molybdate produces joint and bone deformities i s not known. However, we recently reported that molybdate decreases th e sulfation of acetaminophen in rat liver. Therefore, the purpose of t he present study was to determine the effect of molybdate on the sulfa tion of glycosaminoglycans (GAGs) and whether manganese-induced joint and bone deformities might be due to this mechanism. Molybdate (15 mmo l/kg, po) did not alter total GAG content in patella and articular car tilage of rats assayed 24 hr after administration. Nevertheless, [S-35 ]sulfate uptake into both patella and articular cartilage was decrease d dramatically (70 and 50%, respectively) by molybdate. Molybdate did not affect GAG chain elongation, as there was no effect of molybdate o n [H-3]glucosamine uptake into patella cartilage. These results indica te that molybdate impairs sulfation of GAGs. In an attempt to determin e the mechanism of the molybdate-induced decrease in GAG sulfation, th e effect of molybdate and sulfate on the incorporation of sulfate into GAGs was examined in vitro using monolayer chondrocyte cultures. Moly bdate reduced the sulfation of GAGs in chrondrocytes in vitro, but onl y at concentrations higher than the blood concentration of molybdate i n vivo that decreased GAG sulfation. Molybdate given in vivo decreases plasma sulfate to levels, which when used in vitro, decreases GAG sul fation. Therefore, molybdate treatment decreases sulfate availability and the sulfation of glycosaminoglycans. (C) 1996 Academic Press, Inc.