Rabbit articular chondrocytes were incubated with recombinant transforminggrowthiactor-p, (rhTGF-P,) and its effect on newly synthesized proteoglycan measured. rhTGF-P, stimulated proteoglycan synthesis at a concentration as low as 5 ngiml without further increases in radiosulfate incorporation up to 50 ngiml.
The quantitative increase in radiosulfate incorporation in rh-TGF-P, -treated chondrocytes was greater in the cell-associated culture compartment than in the medium compartment. rhTGF-P, promoted an increased proteoglycan retention in the cell-associated compartment as evidenced by an increase in the t% of retention from 8 h to 11 h. Specific enhanced synthesis of [35S]-methioninelabeled core proteins was seen in rh-TGF-fi-treated chondrocytes. rh-TGF-P, increased the synthesis of the 2 core proteins derived from hydrodynamically large proteoglycans. They possessed apparent molecular weights of > 480 kD and 390 kD after 3-5% acrylamide gel electrophoresis. A compartmental analysis revealed that the cell-associated culture compartment contained only the larger of the 2 core proteins derived from large proteoglycans. Two other core proteins with apparent molecular weights 52 kD and 46 kD were also stimulated by rhTGF-P,.
These results indicated that TGF-P probably plays a significant role in stimulating proteoglycan core protein synthesis in articular chondrocytes and therefore may be an important growth factor in the restoration of cartilage extracellular matrix after injury.