In osteoarthrosis, the major and central changes occur in the hyaline articular cartilage. Remodeling and repair of the joint structure often accompany the progression of this disease. To provide a basis for comparison to the pathological situation, we propose to investigate the basic mechanisms that regulate extracellular matrix production in normal cartilage chondrocytes. The approach taken will be to investigate the factors and the mechanisms which control the expression of specific extracellular matrix genes. Questions asked are: What factors control the expression of genes in the mature chondrocyte? At what level of biosynthesis do these effectors act? Are there subpopulations of chondrocytes with differing capacities for biosynthesis? A view of chondrocyte development is emerging which is very different from that traditionally held: that is, it appears that chondrocytes isolated from different tissues, at different ages and from different species have quite variant capacity for gene expression within the confines of what was traditionally considered a chondrocyte: production of type II collagen and high molecular weight, cartilage specific, chrondroitin sulfate proteoglycan. The technologies of recombinant DNA will be used to study gene expression in cultured articular chondrocytes. A model system has been developed in which bovine articular chondrocytes in culture can be used to determine the biosynthetic capability of the cells. Recently we have used this system to show that ascorbic acid can change the predominant type of collagen synthesized. Using specific DNA probes for types I and II collagen mRNAs, we have shown that these cultures can quite readily change the type of collagen mRNA synthesized. We propose to elucidate the mechanisms for this change in mRNA quantities and determine the effects of other factors such as epidermal growth factor, fibroblast growth factor, and insulin-like growth factors, all known to influence matrix synthesis in cartilage. These findings may be extremely significant to the concept of cartilage as an anlage to bone, in "aging" joint cartilage and in diseased cartilage.