In this study an <i>in vitro</i> model was used to simulate joint trauma by subjecting explants of articular cartilage to a single impact load using a specially designed drop-tower loading machine for which two different loading attachments were developed. The aim was to compare the biophysical effects of impact loading on bovine and human cartilage. The proteolytic lysomal enzyme, cathepsin B and the proinflammatory mediators, prostaglandin E₂ (PGE₂) and nitric oxide (NO) have been implicated in the degradation of cartilage following trauma. This study aimed to investigate the role of these degradatory mediators. Human cartilage was found to be less damaged than bovine after impact and the type of loading attachment affected the nature of the damage observed. Following an impact load on human cartilage explants, the levels of glycosaminoglycans (GAGs), a measure of cartilage breakdown, in the culture medium and the percentage of apoptotic chondrocytes were significantly increased. The levels of pro-cathepsin B were significantly increased in the culture medium compared to unloaded controls. Addition of human cystatin C and the synthetic cathepsin B inhibitor, CA-074Me, reduced this release. However these inhibitors had no effect on the release of GAGs or the levels of apoptosis following impact. A marked increase in PGE₂ and NO was measured in the medium following an impact load, which was reduced by the selective cyclooxygenase-2 (COX-2) inhibitor, celecoxib, and the non-selective inhibitor, indomethacin. These inhibitors reduced chondrocyte apoptosis but no change was observed in the release of GAGs from the explants. This <i>in vitro</i> study indicates that cell viability and matrix degeneration are separately regulated and that it is unlikely that cathepsin B or COX-2 inhibition alone would slow down or prevent the development of secondary osteoarthritis.

Thesis (Ph. D.)--University of New South Wales, 2004. / Also available online.

Thesis (Ph.D.)--Aberdeen University, 2008. / Title from web page (viewed on Apr. 21, 2009). Includes bibliographical references.

Thesis (Doctoral)--Department of Cell and Molecular Biology, Lund University, Sweden. / Added t.p. with thesis statement inserted. Includes bibliographical references.

Thesis (Doctoral)--Department of Cell and Molecular Biology, Lund University, Sweden. / Added t.p. with thesis statement inserted. Includes bibliographical references.

Thesis (Ph. D.)--University of Missouri--Columbia, 2004. / Typescript. Vita. Includes bibliographical references. Also issued on the Internet.

Thesis (Ph. D.)--University of Missouri--Columbia, 2004. / "July 2004." Typescript. Vita. Includes bibliographical references. Also issued on the Internet.