EFFECT OF INSULIN-LIKE GROWTH FACTOR-I ON THE SYNTHESIS AND DISTRIBUTION OF LINK PROTEIN AND HYALURONAN IN EXPLANT CULTURES OF ARTICULAR-CARTILAGE

Addition of 20% (v/v) fetal calf serum or insulin-like growth factor-I (IGF-I; 20 ng/ml) to the medium of explant cultures of adult articular cartilage resulted in an increased rate of synthesis of the three components of the proteoglycan aggregate - namely link protein, hyaluronan and aggrecan. Fetal calf serum also stimulated the synthesis of other matrix proteins by articular cartilage compared with tissue maintained in medium alone or medium containing IGF-I. Although addition of fetal calf serum or IGF-I to the culture medium of cartilage explant cultures stimulated both hyaluronan and aggrecan synthesis, no change in the distribution of these two macromolecules between tissue and medium was observed. Approx. 50% of the newly synthesized hyaluronan was retained by the tissue compared to 93% of the labelled aggrecan. Culture conditions had some influence on the distribution of link protein, in cultures maintained in medium alone or in medium containing IGF-I, less than 12% of the newly synthesized link protein was lost to the medium of the cultures. However, in cultures maintained with fetal calf serum between 25% and 19% of the radiolabelled link protein was lost from the matrix of the explants. This work suggests that the chondrocyte synthesizes the macromolecules that make up the proteoglycan aggregate in a co-ordinated manner, thereby retaining the relative amounts of each component of this functionally important complex.