Articular cartilage is a unique tissue both in structure and function. It is avascular of low cell density, and its cells exhibit a low metabolic activity. The pathologies involving this tissue may be closely associated with the inability of chondrocytes to repair a lesion. The extracellular matrix which affords the mechanical rigidity and structure to cartilage is composed almost exclusively of collagen (Type II) and proteoglycans. Since the chondrocytes are responsible for their synthesis it becomes essential to understand their metabolism in normal and diseased situations. What regulated their activity? What causes these cells to so readily lose their ability to synthesize tissue specific macromolecules in culture? Why are these cells so sensitive to environmental changes? What can stimulate the expression of their normal phenotype? Our studies will involve the study of normal and osteoarthritic human cartilage, as well as rabbit articular cartilage from various ages in organ and cell culture. How much collagen and what types (II, I, III & x) do they synthesize? How does the extracellular environment (media, O2 tension, time in culture, etc.) affect these parameters? Is cartilage a homogeneous tissue? (Cloning and cell-fractionation may answer this question.) Does the collagen framework turn over? At what rate? How does the matrix affect cell function and vice versa? How do lymphocytes, macrophages, their metabolic by-products, collagen-degradation peptides and proteoglycan fragments, affect chondrogenic activity?