ENHANCED SULFATED-PROTEOGLYCAN CORE PROTEIN-SYNTHESIS BY INCUBATION OF RABBIT CHONDROCYTES WITH RECOMBINANT TRANSFORMING GROWTH FACTOR-BETA-1

Rabbit articular chondrocytes were incubated with recombinant transforming-growth-factor-beta-1 (rhTGF-beta-1) and its effect on newly synthesized proteoglycan measured. rhTGF-beta-1 stimulated proteoglycan synthesis at a concentration as low as 5 ng/ml without further increases in radiosulfate incorporation up to 50 ng/ml. The quantitative increase in radiosulfate incorporation in rh-TGF-beta-1-treated chondrocytes was greater in the cell-associated culture compartment than in the medium compartment. rhTGF-beta-1 promoted an increased proteoglycan retention in the cell-associated compartment as evidenced by an increase in the t1/2 of retention from 8 h to 11 h. Specific enhanced synthesis of [S-35]-methionine-labeled core proteins was seen in rh-TGF-beta-1-treated chondrocytes. rh-TGF-beta-1 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-beta-1. These results indicated that TGF-beta 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.