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The role of polysaccharide-protein interactions in the organisation and structure of normal and diseased cartilage

Dr M-P. Van Damme

Models of cartilage repair

Cartilage, which covers the articulating joint surfaces of bones, plays an important role in the mechanics of normal joint movement. It is composed of sparsely distributed cells (chondrocytes) embedded in an extracellular matrix composed of a three dimensional mesh of collagens, various proteins/glycoproteins and large water retaining proteoglycans (PGs) which carry negatively charged polysaccharides called glycosaminoglycans (GAGs). The relative content and nature of GAGs change with age, depth and metabolic state of the cartilage. In diseases such as arthritis, there is a loss of GAGs from the cartilage matrix, leading to degeneration and loss of cartilage function.

The ability of chondrocytes to repair damage and loss of articular cartilage by proliferation and deposition of a new and durable matrix is limited. Recently, several models of cartilage repair have been proposed; in one such model, the "Autologous Chondrocyte Transfer" technique (ACT), cells are retrieved from healthy articular cartilage, allowed to proliferate in culture in order to supply adequate cell numbers and reimplanted into articular cartilage defects. However, to date the ACT technique presents some major limitations as chondrocytes grown in culture have a propensity to dedifferentiate to the fibroblast phenotype. Such dedifferentiation will lead to the synthesis of a matrix with biochemical and biomechanical properties different to those found in the tissue of origin. If the ACT technique is to be used in humans as a model of cartilage repair, it is essential to develop an "optimum" culture system whereby cells retain their phenotype and synthesize an appropriate matrix.

Research activities: We have successfully developed an in vitro cell culture system where chondrocytes are grown and maintained in collagen gels for several weeks. Such system can be manipulated to study the effect, on the synthesis of the matrix, of various compounds such as growth factors. The goat is currently used as an animal model but the.studies will be extended to cartilage repair in humans.

Project area

  1. The role of growth factors on the synthesis of proteoglycans and collagens by chondrocytes grown in collagen gels (Dr. Marie-Paule Van Damme and A/P. Barry Oakes, Anatomy).

  2. The role of polysaccharide-protein interactions in the organisation and structure of normal and diseased cartilage (Dr. Marie-Paule Van Damme and Dr. Peter Stanton, Prince Henry's Institute for Medical Research).