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

• Published in: Journal of biomedical materials research 1999-01, Vol.44 (1), p.63-72
• Main Authors: Blanquaert, F., Barritault, D., Caruelle, J.-P.
• Format: Article
• Language: English
• Subjects: 3T3 Cells; Agents; Alkaline Phosphatase - analysis; Animal cell culture; Animals; Biological and medical sciences; Biosynthesis; Bone Morphogenetic Protein 2; Bone Morphogenetic Proteins - pharmacology; Catalyst activity; Cell Differentiation - drug effects; Cell Division - drug effects; Cyclic AMP - metabolism; Dextrans - pharmacology; DNA; DNA - biosynthesis; DNA synthesis; Enzymes; Fibroblast Growth Factor 2 - pharmacology; Genetic engineering; Growth Substances - pharmacology; heparan-like molecules; Heparin - metabolism; heparin-binding growth factors; Hormones; Kinetics; Medical sciences; Mice; osteoblast; Osteoblasts - cytology; Osteoblasts - drug effects; Osteoblasts - physiology; Parathyroid Hormone - pharmacology; phenotype expression; Polysaccharides; Recombinant Proteins - pharmacology; Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases; Technology. Biomaterials. Equipments; Transforming Growth Factor beta - pharmacology
• ISSN: 0021-9304; 1097-4636
• DOI: 10.1002/(SICI)1097-4636(199901)44:1<63::AID-JBM7>3.0.CO;2-S

Heparan‐like polymers derived from dextran, named RGTA, were shown to stimulate bone repair in different bone defect models. Like heparin and heparan sulfates, RGTA potentiate in vitro the biological activities of heparin‐binding growth factors (HBGFs), such as fibroblast growth factor (FGF), by stabilizing them against denaturations and by enhancing their binding with cellular receptors. RGTA were postulated to stimulate bone healing by interacting with HBGFs released in the wound site and, subsequently, by promoting the 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 [3H]‐thymidine incorporation into DNA. They enhanced the inhibition of DNA synthesis caused by transforming growth factor‐β (TGF‐β1) and bone morphogenetic protein‐2 (BMP‐2). RGTA alone increased the alkaline phosphatase and parathyroid hormone‐responsive adenylate cyclase activities in MC3T3. RGTA enhanced the stimulation of the alkaline phosphatase activity induced by BMP‐2 and decreased or suppressed the inhibition caused by TGF‐β1 and FGF‐2. Furthermore, RGTA increased the response to parathyroid hormone stimulated by BMP‐2. In conclusion, RGTA stimulate the expression of osteoblast phenotype features alone or in association 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. © 1999 John Wiley & Sons, Inc. J Biomed Mater Res, 44, 63–72, 1999.