Regulation of chondrogenesis by heparan sulfate and structurally related glycosaminoglycans

To test the possible involvement of heparan sulfate proteoglycans in chondrogenesis, we have studied the effect of their major glycosaminoglycan (GAG) component, heparan sulfate, and other structurally related GAGs on chondrogenesis in micromass cultures of chick limb bud mesenchyme (Hamburger-Hamilton stages 23/24). Heparan sulfate and several of its analogs (heparin, dermatan sulfate, and dextran sulfate) were found to significantly stimulate cartilage nodule formation; in addition, heparan sulfate and heparin also promoted nodule growth. Chondroitin sulfate did not stimulate chondrogenesis. The activity of the GAGs was dependent on their dose, molecular size, charge, and chemical structure. Similar effects were also observed in micromass cultures derived from stage 25 embryonic wing-tip subridge mesoderm, an enriched population of chondroprogenitor cells. The time of action of the GAGs during culture suggested their involvement in post-cell aggregation events of chondrogenesis, such as the initial expression of the chondrocyte phenotype or the growth of cartilage nodules.