hyaluronate, in chondrocytes

Cartilage proteoglycans are complex macromolecules in which many glycosaminoglycan chains are attached to a protein core. Chondrocytes isolated from the Swarm rat chondrosarcoma have been shown to produce cartilage-type proteoglycans in culture. The proteoglycans are secreted from the cells as monomers, but form aggregates in the culture medium by binding to hyaluronate and a specific link protein (Kimura et al., 1979). All three components of the aggregate are synthesized by the chondrocytes, but it remains to be determined how aggregation is delayed until the components have been secreted from the cells (Hardingham, 1981; Kimura et al., 198 ib). Experiments suggest that link protein may be secreted already bound to the proteoglycan (Kimura et al., 1980), but the pathways of synthesis and secretion of hyaluronate remain unknown. The post-translational modifications of the proteoglycan protein core, which involve the initiation, elongation and sulphation of the chondroitin sulphate chains, occur primarily in the Golgi region of the cell, and with chick chondrocytes it has been shown that monensin is a potent inhibitor of chondroitin sulphate synthesis and sulphation (Tajiri et al., 1980). Monensin is a carboxylic ionophore that interferes with the intracellular pathways of secretory proteins in many different cell types (Tartakoff & Vassalli, 1977, 1978; Uchida et al., 1979). It causes a rapid dilation of the Golgi elements, which may result from partial Na+/K+ equilibration across the membranes (Tartakoff& Vassalli, 1978). The present study examines further the effects of monensin on proteoglycan and hyaluronate synthesis in chondrocytes.