Enhancement of the biological activity of BMP-2 by synthetic dextran derivatives.
In the present study, we explored the binding capacity of synthetic heparin-like dextran derivatives to recombinant human bone morphogenetic protein 2 (BMP-2), a heparin-binding osteoinductive growth factor. Affinity electrophoresis analysis provided evidence that carboxymethylated dextran polymers grafted with high amounts of benzylamide groups (named DMCB) interact with BMP-2. The capability of such polysaccharides to potentiate the growth factor biological activity was then investigated. In vitro, DMCB dose-dependently promoted osteoblast differentiation induced by BMP-2 in C2C12 myoblasts more efficiently than heparin. A screening study provided evidence that the potentiating effects of the dextran derivatives on the BMP-2-induced alkaline phosphatase activity improved with their benzylamide groups content and, therefore, with their affinity for the growth factor. The biological activity of BMP-2 was monitored in the culture medium after 6 days using C2C12 cells (containing a BMP sensitive luciferase reporter gene). Like heparin, DMCB sustained the biological activity of the growth factor; this result suggests that the formation of the BMP-2/DMCB complex may protect the protein from being inactivated. In rats in vivo, DMCB also stimulated ectopic calcification mediated by BMP-2. These data indicate that dextran-based polysaccharides prolong the half-life of the growth factor and promote its biological activity.
Degat
Marie-Christelle
MC
Laboratoire de Recherches Orthopediques (B2OA), CNRS UMR 7052 (SPI), Paris 7 University, Paris, France.
Dubreucq
Guy
G
Meunier
Alain
A
Dahri-Correia
Latifa
L
Sedel
Laurent
L
Petite
Herve
H
Logeart-Avramoglou
Delphine
D
D000818:Animals; D055396:Bone Morphogenetic Protein 2 / Q000494:pharmacology*; D002113:Calcification, Physiologic; D018929:Cell Culture Techniques; D002454:Cell Differentiation / Q000187:drug effects; D003911:Dextrans / Q000494:pharmacology*; D004357:Drug Synergism; D006493:Heparin; D006801:Humans; D032446:Myoblasts / Q000166:cytology / Q000187:drug effects; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects*; D011134:Polysaccharides / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats
D055396:Bone Morphogenetic Protein 2; D003911:Dextrans; D011134:Polysaccharides; D006493:Heparin