During aging, macroscopically normal articular cartilage weakens, with a decrease in tensile stiffness and strength. As cartilage degeneration, often age-associated, progresses to osteoarthritis, cartilage displays classical changes of increased fragmentation of aggrecan and the collagen network with a decrease in tissue proteoglycan content, cell cloning near fissures, hypocellularity in other areas of tissue, and further tensile weakening. While the age-related degenerative changes appear to precede osteoarthritic changes, the exact sequence of pathogenic events is unclear. It was the aim of this dissertation to delineate the extent and time-sequence of these changes to give insight into the mechanisms underlying age-associated degeneration and osteoarthritis.

In particular, changes in articular cartilage with aging and osteoarthritis may be due primarily to (1) mechanical alteration of the surface, (2) enzymatic degradation of extracellular matrix components, or (3) loss and disorganization of cells. To elucidate the time sequence of such changes, and their relevance to in vivo processes, the surface structure, composition, and function of human cartilage samples displaying a normal structure, minor fibrillation (early degeneration, from non-osteoarthritic joints), and moderate fibrillation (from osteoarthritic joints) were analyzed. Age-associated tensile weakening of the superficial zone pointed to a role of surface wear as an initiator in early cartilage degeneration, with cell loss and matrix degradation as downstream events. Tensile weakening in mildly and moderately fibrillated cartilage highlighted the combined roles of surface wear, cell loss, matrix degradation, and collagen network remodeling in the progression of osteoarthritis. Detailed two- and three-dimensional study of the density and organization of chondrocytes of the superficial zone revealed a mild age-associated decrease in cell density and a noteable loss of cells and cell organization in early cartilage degeneration. IL-1-induced enzymatic degradation of articular cartilage was quantified as an initial loss of glycosaminoglycan followed by degradation of the collagen network. Cartilage weakening occurred at a time subsequent to glycosaminoglycan loss and parallel to collagen degradation, suggesting a causal role for collagen degradation in tensile weakening.

The information obtained from these studies gave insight to the role of, and relationship between, cells and matrix in cartilage aging and osteoarthritic disease.