**4. Variation in the CS Chain Fine Structure with Development and Pathology in Health and Disease**

Several years ago [58,64,73], MAbs 3-B-3(−) and 7-D-4 were shown to identify chondrocyte-clusters in pathological (osteoarthritic) canine and human articular cartilage. At that time, which pre-dated knowledge of stem/progenitor cell niches in tissues, these cell-clusters were considered a classical feature of the onset of late stage degenerative joint disease and were interpreted to indicate a failed, late-stage, response to replace PGs in a matrix extensively degraded by matrix proteases. An alternative explanation of this cellular phenomenon however has now emerged. It is now believed that these "chondrocyte clusters" arise from adult stem/progenitor cell niches [74–77]. The 3-B-3(−), 4-C-3 and 7-D-4 CS sulphation motifs also occur in foetal development and are markers of anabolic processes in transitional tissues (Figure 2a,d). An important feature of the stem/progenitor cell niche is the sulphation of the PG GAG side chains (Figure 1a,f). Variable expression of GAG sulphotransferases and glycosyl transferases in stem/progenitor cell niches (Figure 2a,c,d) supports such an interpretation [78–80]. Cell clusters have also been shown to express Notch 1 and CD166, biomarkers that are synonymous with the stem cell niche [74,81].
