On the Sulfation Pattern of Polysaccharides in the Extracellular Matrix of Sheep with Chondrodysplasia

OBJECTIVE Chondroitin sulfate is the major sulfated polysaccharide attached to the core protein, aggrecan, in the hyaline cartilage matrix. Sulfation of the cartilage matrix polysaccharide is vital for normal matrix integrity and compressive stiffness of the tissue and is therefore crucial to normal cartilage formation and consequently to endochondral ossification. Several forms of chondrodysplasia, a condition resulting in clear macroscopic deficiencies in the mechanical properties of the cartilage and characterized by reduced levels of sulfate, have been identified in both human beings and animals. DESIGN In this study, the authors used capillary electrophoresis to investigate the sulfation state of extracted chondroitin sulfate polymers. RESULTS Significantly, cartilage from affected sheep had a lower ratio of the chondroitin-derived enzymatically liberated disaccharides Δdi-mono4S to Δdi-mono6S, demonstrating reduced levels of chondroitin 4-sulfate, but not chondroitin 6-sulfate, in chondrodysplastic sheep compared to age-matched controls at all ages measured. CONCLUSION This supports the hypothesis that a difference in chondroitin sulfate disaccharides is detectable in affected newborn lambs prior to the development of lesions.