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Abstract
Osteoarthritis is the clinical end-point of a degenerative process, an early stage of which is the degradation of articular cartilage. The exact processes which lead to the breakdown of cartilage have not yet been determined, but mechanical factors must play some role. This thesis is concerned with the relationship between the mechanical properties and structure of articular cartilage and with the potential roles of some proteolytic enzymes in the development of arthritis. Specimens of cartilage from the human hip, knee and ankle joints were treated with specific enzymes, which had been identified in synovial joints and whose degradative action on the microstructure of cartilage had been established. The effects of the structural changes produced by the enzymes on the compressive and tensile properties of cartilage were determined and then discussed. Results showed that degradation of the proteoglycan alone in cartilage decreased the viscous damping, increased the creep component of compression but did not alter the elastic stiffness in compression. In tension the tangent modulus at low stress levels was reduced but the tangent modulus at high stresses and the fracture stress itself were not significantly reduced. Degradation of collagen, as well as proteoglycan, decreased the elastic stiffness in compression and the tensile tangent modulus at high stresses as well as the tensile fracture stress. These results strongly suggested that the elastic component of the mechanical response of cartilage is dependent on the collagen fibres while the time-dependent component of the response in the form of viscous damping and creep depends on the proteoglycan in cartilage. Leukocyte elastase is an enzyme which is present in inflamed joints and is capable of degrading collagen fibres as well as proteoglycans. However, despite subsequent treatment with denaturing agents, it was not possible to release a significant quantity of collagen from the matrix of cartilage following treatment with leukocyte elastase. This suggested that, even though the main intermolecular cross-links had been disrupted by elastase, the molecules and fibrils were still bound together by other cross-links which were not attacked by this enzyme. The potentially important role of leukocyte elastase in the initial stages of rheumatoid arthritis and osteoarthritis is discussed.
