Inhibition of Proteoglycan Biosynthesis Decreases the Calcification of Chondrocyte Cultures

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Abstract
In order to determine the role of proteoglycan in the calcification of cartilage, the effects on calcifying chondrocyte cultures of treatments that disrupt proteoglycan biosynthesis have been studied. Treatment of secondary cultures of embryonic chick chondrocytes with non-toxic concentrations of the β-xyloside p-nitrophenyl β-D-xylopyranoside (PNPX) resulted in dose-dependent inhibition of both proteoglycan and mineral deposition. Based on the expression of Type X collagen, however, PNPX is also a potent inhibitor of chondrocyte differentiation. Under-sulfation of proteoglycans was effected by growth of chondrocyte cultures in sulfate-depleted medium. Growth in low-sulfate medium did not significantly affect the growth or differentiation of these cultures, but caused an approximate two-fold decrease in mineral content compared to cultures grown in normal medium. These findings indicate that disruption of proteoglycan biosynthesis in chondrocyte cultures results in decreased levels of calcification. Therefore, proteoglycans appear to function as promoters of chondrocyte calcification.