|Our research is involved with the molecular basis of the repair of damaged articular cartilage and bone. This is an emerging area in arthritis research, as most labs had concentrated on mechanisms and causes of articular damage but the causes of the chronic forms of arthritis remain unknown.
An important part of cartilage structure and function is related to large, extracellular glycoconjugates such as the proteoglycans. We are specifically interested in the metabolic control of cartilage glycoconjugates by the group of small peptides that are known to modulate the growth and differentiation of cartilage, of which Transforming Growth Factor-_ (TGF-_) is the prototype. We use tissue culture models, mainly of cartilage, to study this area. The interested student may participate in one of several projects described below.
We have recently discovered that cultured articular chondrocytes elaborate a very high molecular weight anionic glycoconjugate (HMW AG), which is not a proteoglycan, and which is only detectable if the chondrocyte cultures are stimulated with TGF-_. One project in the lab is to further characterize this HMW AG, to determine the distribution of its mRNA in normal and osteoarthritic tissue and its relation to endogenous and exogenous TGF-_, and to investigate its possible function(s). We are also interested in the modification of proteoglycans of cartilage and bone by using what we refer to as a "nutritional approach", which involves feeding the cell cultures (or animals) with appropriately modified, non-toxic substrates. Affinity columns for proteoglycans have been prepared and these can be used to study the behaviour and interactions of the modified proteoglycans. The chemistry of the glycosaminoglycans of the proteoglycans is also being studied, following stimulation of the cultures with TGF-_ and other active peptides. There is also a project on the effect of non-steroidal anti-inflammatory drugs on proteoglycan synthesis by chondrocytes and clinical projects on the use of diphosphonates in preventing osteoporosis