The familial disease of
hereditary multiple exostoses is characterized by abnormal skeletal
deformities requiring extensive
surgical procedures. In
hereditary multiple exostoses patients there is a shortage in the pericellular
glycosaminoglycan (GAG) of
heparan sulfate (HS), related to defective activity of HS
glycosyltransferases, mainly in the pericellular regions of chondrocytes. This study searched for a novel approach employing
xylosides with different aglycone groups priming a variety of GAG chains, in attempting to alter the GAG compositional profile. Cell cultures of patients with
osteochondroma responded to p-nitrophenyl β-D-xyloside by a significant increase in total GAG synthesis, expressed mainly in the extracellular domains, limited to
chondroitin sulfate). The different β-D-
xylosides, in addition to increasing the synthesis of extracellular GAGs, led to a significant depletion of the intracellular GAG domains. In mouse chondrocyte cultures, β-D-
xylosides with different aglycones created a unique distribution of the GAG pools. Of special interest was the finding that the
naphthalene methanol β-D-xyloside showed the highest absolute levels of HS-GAGs in both extracellular and intra-pericellular moieties compared with other β-D-
xylosides and with controls without xyloside. In summary, β-D-
xylosides can be utilized in chondrocyte cultures to modify the distribution of GAGs between the extracellular and intracellular compartments. In addition,
xylosides may alter the profile of specific GAG chains in each moiety.