Effects of heparan-like polymers associated with growth factors on osteoblast proliferation and phenotype expression

Heparan-like polymers derived from dextran, named RGTA, were shown to stimu late bone repair in different bone defect models. Like heparin and heparan sulfates, RGTA potentiate in vitro the biological activities of heparin-bin ding growth factors (HBGFs), such as fibroblast growth factor (FGF), by sta bilizing them against denaturations and by enhancing their binding with cel lular receptors. RGTA were postulated to stimulate bone healing by interact ing with HBGFs released in the wound site and, subsequently, by promoting t he proliferation and/or differentiation of cells implicated in this process . We examined the effects of RGTA alone and associated with HBGFs on MC3T3- E1 osteoblastic cell proliferation and differentiation. RGTA inhibited cell proliferation, as measured by [H-3]thymidine incorporation into DNA. They enhanced the inhibition of DNA synthesis caused by transforming growth fact or-beta (TGF-beta 1) and bone morphogenetic protein-2 (BMP-2). RGTA alone i ncreased the alkaline phosphatase and parathyroid hormone-responsive adenyl ate cyclase activities in MC3T3. RGTA enhanced the stimulation of the alkal ine phosphatase activity induced by BMP-2 and decreased or suppressed the i nhibition caused by TGF-beta 1 and FGF-2. Furthermore, RGTA increased the r esponse to parathyroid hormone stimulated by BMP-2. In conclusion, RGTA sti mulate the expression of osteoblast phenotype features alone or in associat ion with HBGFs. The ability to promote the differentiation of bone-forming cells is a potential explanation of the stimulating effect of RGTA on bone repair. (C) 1999 John Wiley & Sons, Inc.