[Evaluation of the osteoinductive potential of genetically modified BMP-2 variants].
BACKGROUND
The alteration of the N-terminal amino acid sequence of BMP-2 allows modification of heparin binding of the new protein. This leads to a change in the local retention time at the site of implantation. Mutants with increased (T3, T4) and with no binding (EHBMP-2) to heparin were assessed for their osteoinductivity in vivo and compared with the wild type BMP-2.


METHODS
Cylindrical collagenous carriers (diameter = 5 mm, height = 10) were loaded with different concentrations (0.25-4 micro g) of the proteins. Following intramuscular implantation into the hind legs, the bone formation was measured in radiographic follow-ups. After 28 days the newly formed bone was characterized histologically.


RESULTS
Elimination of the heparin binding leads to massive reduction in osteoinductivity. On the other hand, an increase in the heparin binding leads to enhancement in the osteoinductive properties, resulting in faster bone formation with a higher yield.


CONCLUSIONS
It could be shown for the first time that modifications of BMP-2 by gene technology can lead to proteins with enhanced binding to components of the extracellular matrix. The resulting prolonged retention time at the implantation site results in an increased osteoinductivity compared with the wild type.
Würzler
K K
KK
Klinik und Poliklinik für Mund- Kiefer- und Gesichtschirurgie, Bayerische Julius-Maximilians-Universität Würzburg. kristian.wuerzler@t-online.de
Emmert
J
J
Eichelsbacher
F
F
Kübler
N R
NR
Sebald
W
W
Reuther
J F
JF
D000595:Amino Acid Sequence / Q000235:genetics*; D000818:Animals; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins / Q000235:genetics* / Q000494:pharmacology*; D001861:Bone Regeneration / Q000187:drug effects*; D018786:Bone Substitutes; D002352:Carrier Proteins / Q000235:genetics*; D020099:Coated Materials, Biocompatible; D003094:Collagen; D004305:Dose-Response Relationship, Drug; D005821:Genetic Techniques; D014644:Genetic Variation / Q000235:genetics*; D006801:Humans; D008297:Male; D008852:Microradiography; D008856:Microscopy, Fluorescence; D009154:Mutation / Q000235:genetics*; D016348:Osseointegration / Q000187:drug effects*; D010443:Peptide Chain Termination, Translational / Q000235:genetics; D019736:Prostheses and Implants; D051381:Rats; D017207:Rats, Sprague-Dawley; D016212:Transforming Growth Factor beta
C525718:BMP2 protein, human; C525720:Bmp2 protein, rat; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins; D018786:Bone Substitutes; D002352:Carrier Proteins; D020099:Coated Materials, Biocompatible; D016212:Transforming Growth Factor beta; D003094:Collagen