Teemu Långsjö Collagen Network of the Articular Cartilage

Degenerative joint disease is a major cause of functional disability and pain affecting globally hundreds of millions people. In the western countries, osteoarthritis is a major joint disease most often affecting people over 65 years of age. Aging, joint loading, articular cartilage injuries, obesity, and genetic factors are known to influence the development of osteoarthritis. In osteoarthritis, the loss of proteoglycans is known to lead to a reduction of stiffness in the articular cartilage. The disruption of the collagen network especially in the superficial zone of the articular cartilage leads, in addition to the reduction in the proteoglycan concentration, also to an increase in the water content of the articular cartilage. The swelling of the articular cartilage itself increases the vulnerability of articular cartilage and triggers a vicious cycle that leads gradually to total loss of the hyaline cartilage. Ultimately this means that the eburnated bone ends start to rub against each other. The quantitative ultrastructural analysis of the collagen network of articular cartilage has proved to be a challenging task. One goal of this thesis was to develop and validate a stereologic electron microscopic analysis method for the examination of the articular cartilage collagen network. This study indicated that the indirect, zonal estimation of the collagen volume and surface densities using the collagen length density and the average collagen fibril diameter, or the average of the second powers of the diameters, represented a minimally biased and sensitive method for the ultrastructural analysis of the collagen network. The technique was also used to analyse the hyaline cartilage collagen phenotypes of different mice lines harboring gene mutations affecting either the synthesis or the processing of the collagen molecules. The method proved to be sensitive in revealing the differences in the stereological estimates between the transgenic and control mice groups. The technique was also used to characterize the collagen network of the repair tissue in porcine articular cartilage after autologous chondrocyte transplantation which had been used to repair the full-thickness local articular cartilage defect. It was shown that after one year, the repair tissue contained type-II-like collagen fibrils that appeared to form an equally dense network as in the control cartilage, but the fibrils were more randomly oriented. National Library of Medicine Classification: QU 55.3, WE 300, WE 348 Medical Subject Headings: Cartilage, Articular/ultrastructure; Collagen/analysis; Microscopy, Electron/methods; Osteoarthritis