THE EFFECTS OF ACID GLYCOSAMINOGLYCANS ON NEONATAL CALVARIAN CULTURES- A ROLE OF KERATAN SULFATE IN MORQUIO-SYNDROME

Morquio syndrome (mucopolysaccharidosis IV) presents with multiple bon e dysplasia and is characterized by the inability to degrade keratan s ulfate due to deficient N-acetylgalactosamine-6-sulfate sulfatase in M orquio A syndrome and deficient beta-D-galactosidase in Morquio B synd rome. The aim of our study was to investigate into the pathogenetic me chanism as it is not clear whether the accumulation of keratan sulfate is toxic for osteoblasts or inhibits osteoblast activity as e.g. bone resorption. The glycosaminoglycans keratan sulfate, heparan sulfate, dermatan sulfate, chondroitin-4,6-sulfate and hyaluronic acid were tes ted in rat neonatal calvarian cultures for their effects on bone resor ption, osteoblast activity and toxicity. Bone resorption was evaluated by calcium release into the medium, osteoblast activity by the determ ination of alkaline phosphatase and toxicity by measuring lactate dehy drogenase in the culture media. Keratan sulfate had no effect on bone resorption but inhibited osteoblast activity at the low, nontoxic conc entration of 10 ng per mi organ culture supernatant significantly (p<0 .05). At a concentration of 100 ng per mi keratan sulfate revealed tox ic effects as reflected by significantly (p<0.05) elevated lactate deh ydrogenase activity. None of the other glycosaminoglycans inhibited os teoblast activities. Heparan sulfate showed at toxic levels (10 mu g p er mi supernatant) significantly increased bone resorption (p<0.05) ac companied by increased alkaline phosphatase activity. The specific ker atan sulfate effects of inhibiting osteoblast activity and toxicity to wards bone, which were never tested before, suggest a role for this gl ycosaminoglycan in the pathogenesis of bone dysplasia in Morquio syndr ome.