[Comparison of the osteogenic activity of bone morphogenetic protein (BMP) mutants].
BACKGROUND
Modification of the heparin binding site by alteration of the amino acid sequence of bone morphogenetic protein-2 (BMP-2) results in a change in the local retention time. The purpose of this study was to compare the osteogenic activity of T3 and T4, two mutants with increased binding capacity to heparin, and B2GDF-5 a mutant resulting from the fusion of the n-terminal amino acid sequence of BMP-2 and the c-terminal sequence of GDF-5 with wild-type BMP-2 in vivo.


METHODS
The proteins were coupled to an equine-derived collagen carrier and implanted in standardized critical size calvarial defects in adult rats. After 28 days, bone formation was evaluated radiographically and the new bone was characterized histologically.


RESULTS
Proteins T3 and T4 showed a higher osteogenic activity than BMP-2. Less new bone formation was observed with GDF-5 and B2GDF-5 than with-type BMP-2. No difference in bone formation was observed between GDF-5 and B2GDF-5.


CONCLUSIONS
Increased heparin binding capacity enhances osteogenic activity of BMP-2 in vivo. This might be due to a longer retention period in the tissue and thus better bioavailability. Replacement of the N-terminal amino acid sequence of GDF-5 by the corresponding sequence of BMP-2 did not result in an increased osteogenic activity as heparin binding capacity is not the main reason for the bioavailability of GDF-5.
Depprich
R
R
Klinik für Kiefer- und Plastische Gesichtschirurgie, Heinrich-Heine-Universität Düsseldorf.
Handschel
J
J
Sebald
W
W
Kübler
N R
NR
Würzler
K K
KK
D000595:Amino Acid Sequence / Q000235:genetics; D000818:Animals; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins / Q000235:genetics* / Q000493:pharmacokinetics / Q000494:pharmacology; D002356:Cartilage / Q000187:drug effects; D005109:Extracellular Matrix / Q000378:metabolism; D055428:Growth Differentiation Factor 5; D006736:Horses; D066298:In Vitro Techniques; D008297:Male; D009154:Mutation / Q000235:genetics*; D010012:Osteogenesis / Q000187:drug effects; D010446:Peptide Fragments / Q000235:genetics* / Q000493:pharmacokinetics / Q000494:pharmacology; D051381:Rats; D011994:Recombinant Proteins / Q000493:pharmacokinetics / Q000494:pharmacology; D013329:Structure-Activity Relationship; D016212:Transforming Growth Factor beta / Q000235:genetics* / Q000493:pharmacokinetics / Q000494:pharmacology
C525720:Bmp2 protein, rat; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins; D055428:Growth Differentiation Factor 5; D010446:Peptide Fragments; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta