**5. E**ff**ects of Modulation of CS Sulphation on Gene Expression and Cartilage Development**

In chondrocyte cultures, p-nitrophenyl xyloside (PNPX) acts as a competitive acceptor of CS/DS substitution on PG core proteins [82]. PNPX treatment reduces SOX-9, aggrecan and collagen type II gene expression, levels of collagen type II protein synthesis and PG sulphation. It also leads to delayed expression of native CS/DS sulphation motif epitopes and delayed chondrogenic differentiation of bovine MSCs accompanied with reduced tissue development. While the precise role of native CS sulphation motifs identified by MAb 3-B-3(−), 4-C-3, 7-D-4 and 6-C-3 in transitional tissues are not known, they appear to be of importance in the initial stages of chondrogenesis and their distribution patterns indicate they have roles in morphogenetic signalling through the capture and cellular presentation of soluble bioactive molecules (growth factors, morphogens, etc.) of importance in tissue development and morphogenesis [51,58–60,83] (Figure 2a,c,d).
