The effects of beta-D-xyloside on the synthesis of proteoglycans by skeletal muscle: lack of effect on decorin and differential polymerization of core protein-bound and xyloside-linked chondroitin sulfate.

Developing skeletal muscle cells, as both myoblasts and myotubules, synthesize a distinctive large chondroitin sulfate proteoglycan. To probe the role of this proteoglycan in myogenesis, chick embryonic muscle cells in culture were treated with beta-D-xyloside, a compound which interferes with proteoglycan synthesis by acting as an artificial acceptor for glycosaminoglycan synthesis and thereby competing with the proteoglycan core protein. Analysis of the proteoglycans indicates that with increasing concentrations of beta-D-xyloside, synthesis of the chondroitin sulfate proteoglycan is inhibited, with concomitant massive synthesis of xyloside-linked chondroitin sulfate glycosaminoglycans. Xyloside does not appear to inhibit glycosaminoglycan attachment onto the small heparan sulfate and dermatan sulfate proteoglycans which are synthesized in the muscle cultures, even though, because of the mechanism of action of beta-xyloside, these proteoglycans should be affected. At submaximal concentrations of beta-xyloside, there is synthesis of both large chondroitin sulfate proteoglycans and xyloside-linked chondroitin sulfate. The xyloside-linked chondroitin sulfate chains have the same sulfation pattern as the core protein-bound skeletal muscle chondroitin sulfate (90% 6-sulfated isomer), but are much smaller (24,000 vs. 65,000 in molecular weight). The discrepancy in size but identify of sulfation indicates that, although sulfation takes place normally on either the core protein or the xyloside acceptor, termination of glycosylation occurs earlier for xyloside-initiated chondroitin sulfate. In spite of these dramatic effects on chondroitin sulfate proteoglycan synthesis, beta-xyloside elicits no observable effects on in vitro myogenesis. This suggests that the function served by the large chondroitin sulfate proteoglycan is not required in the more simplified environment of the muscle cultures.