[EHBMP-2. Initial BMP analog with osteoinductive properties].
For the first time a non natural BMP-variant (EHBMP-2) with osteoinductive properties was produced by expression in E. coli through specific mutation of the amino acid sequence. The substitution of 12 N-terminal amino acids by a nonsense sequence results in a neglectible affinity of EHBMP-2 to the extracellular matrix. In vitro EHBMP-2 induces dose-dependent cartilage formation in neonatal muscle tissue. Single intramuscular implantation in mice results in the formation of an ossicle with functional active bone marrow. The size of the ossicle depends on the amount of implanted EHBMP-2 and can significantly be increased by the combination with a collagen carrier. The largest bone formation is observed after injection of EHBMP-2 containing collagen suspensions. In rats a stronger osteoinductive activity can be achieved by coupling of EHBMP-2 to collagen discs than by coupling natural BMP-2 to the same collagen carrier. Critical size defects in rats' mandibular angels can be restored by the combination of granular collagenous bone matrix (ICBM) with EHBMP-2. Further investigations have to show whether the altered pharmacokinetics of EHBMP-2 has advantages regarding its therapeutical use and tissue-engineering.
Klinik und Poliklinik für Mund-, Kiefer-, Gesichtschirurgie, Bayerische Julius-Maximilians-Universität Würzburg.
N R
NR
Kübler
K
K
Würzler
J F
JF
Reuther
G
G
Faller
E
E
Sieber
T
T
Kirchner
W
W
Sebald
D019943:Amino Acid Substitution / Q000235:genetics; D000818:Animals; D001857:Bone Matrix; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins / Q000235:genetics / Q000494:pharmacology*; D002642:Chick Embryo; D003094:Collagen; D006801:Humans; D007273:Injections, Intramuscular; D008334:Mandible / Q000601:surgery; D051379:Mice; D008813:Mice, Inbred ICR; D009065:Mouth Rehabilitation; D010012:Osteogenesis / Q000187:drug effects*; D012516:Osteosarcoma; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000494:pharmacology; D016212:Transforming Growth Factor beta; D014407:Tumor Cells, Cultured
C525718:BMP2 protein, human; C525719:Bmp2 protein, mouse; C525720:Bmp2 protein, rat; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta; C499469:recombinant human bone morphogenetic protein-2; D003094:Collagen
EHBMP-2. Erstes BMP-Analog mit osteoinduktiven Eigenschaften.