Fell-Muir Lecture: chondroitin sulphate glycosaminoglycans: fun for some and confusion for others

This review emphasizes the importance of glycobiology in nature and aims to highlight, simplify and summarize the multiple functions and structural complexities of the different oligosaccharide combinatorial domains that are found in chondroitin sulphate/dermatan sulphate (CS/DS) glycosaminoglycan (GAG) chains. For example, there are 1008 different pentasaccharide sequences possible within CS, DS or CS/DS hybrid GAG chains. These combinatorial possibilities provide numerous potential ligand-binding domains that are important for cell and extracellular matrix interactions as well as specific associations with cytokines, chemokines, morphogens and growth factors that regulate cellular differentiation and proliferation during tissue development, for example, morphogen gradient establishment. The review provides some details of the large and diverse number of different enzymes that are involved in CS/DS biosynthesis and attempts to explain how differences in their expression patterns in different cell types can lead to subtle but important differences in the GAG metabolism that influence cellular proliferation and differentiation in development as well as regeneration and repair in disease. Our laboratory was the first to generate and characterize monoclonal antibodies (mAb) that very specifically recognize different ‘native’ sulphation motif/epitopes in CS/DS GAG chains. These monoclonal antibodies have been used to identify very specific spatio-temporal expression patterns of CS/DS sulphation motifs that occur during tissue and organ development (in particular their association with stem/progenitor cell niches) and also their recapitulated expression in adult tissues with the onset of degenerative joint diseases. In summary, diversity in CS/DS sulphation motif expression is a very important necessity for animal life as we know it.