McDowell, Jenny Melinda; (1990) The cell biology of articular cartilage chondrocytes. Doctoral thesis (Ph.D.), University College London.

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Abstract

Degenerative joint disease affects over 40% of the population over 40 years of age, and the incidence increases dramatically with advancing years. However, most of the basic experimental work carried out on articular cartilage uses animal tissue. Because of fundamental biological differences between human and most laboratory animals, extrapolation from animal work to the human situation is very difficult. Therefore, work on human tissue is vital. A key question in the understanding of articular cartilage is how the extracellular matrix is regulated. In order to address this problem, the synthesis of certain matrix components have been mapped both in whole tissue sections and in isolated chondrocytes grown in culture. Antibodies raised to collagen types I and II, keratan sulphate, dermatan sulphate proteoglycan, hyaluronan binding region and link protein were used, in addition to a biochemical probe to localise free hyaluronan sites. In whole tissue sections, age related differences were found in the localisation of keratan sulphate, dermatan sulphate proteoglycan and hyaluronan. In order to gain insights into the control of matrix synthesis, isolated chondrocytes were grown under two culture conditions, low density monolayer and suspension over agarose. This allowed the effects of anchorage dependence and differences in cell shape to be studied. In suspension culture, cells from the surface region of cartilage formed morphologically distinct clusters from those formed by deep region cells, which remained throughout culture. A relationship was shown to exist between cell shape and synthetic ability for collagen, keratan sulphate, dermatan sulphate proteoglycan, proteoglycan monomer and hyaluronan, but not for link protein. In relation to keratan sulphate, two populations of chondrocytes were isolated and grown in culture, one which preferentially synthesised keratan sulphate, and one which did not. This second population was predominantly located in the surface zone of cartilage. We found that whilst suspension culture promoted the synthesis of keratan sulphate, even in cells which do not normally synthesise this component, culture in monolayer inhibited its synthesis. Our results also suggest that in relation to the study of cell sub-populations, the use of a single phenotypic marker is unacceptable, and a range of indicators is required. The observed modulation in phenotype of chondrocytes maintained in culture is discussed in terms of environmental control of gene expression and possible changes in cell symmetry.

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