Augmentation of osseous phenotypes in vivo with a synthetic peptide.
The synthetic peptide B2A2-K-NS augmented the in vitro expression of osseous phenotypes when cells were stimulated with BMP-2, an osteoinductive growth factor. B2A2-K-NS significantly enhanced the effects of BMP-2-induced alkaline phosphatase activity and mineralization. In the absence of BMP-2, B2A2-K-NS did not have an effect on these endpoints. Based on these observations, in vivo studies were conducted to evaluate if B2A2-K-NS could augment osseous phenotypes in an osteoinductive environment in which BMP-2 should be present. In one study, human demineralized bone matrix (DBM) was used to generate an osteoinductive environment and the effects of B2A2-K-NS on ectopic mineralization of subcutaneous implants evaluated. In the second study, a noncritical sized defect in rabbit ulnas with inherent reparative capacity was used as the osteoinductive environment and was treated with or without B2A2-K-NS. In the DBM studies, B2A2-K-NS augmented mineralization as determined using a combination of radiographic analysis and von Kossa staining at 4 weeks postimplant. In the rabbit ulna model, B2A2-K-NS significantly increased the radiographic bone density in the defects compared to carrier-only or no-treatment controls after 6 weeks. Histological staining confirmed that B2A2-K-NS generated a pronounced bone repair response. The results are consistent with the hypothesis that B2A2-K-NS augments osseous phenotypes in an osteoinductive environment, and suggests that B2A2-K-NS may have clinical utility.
Lin
Xinhua
X
BioSurface Engineering Technologies, Inc., 9430 Key West Avenue, Suite 220, Rockville, Maryland 20850, USA. xlin@biosetinc.com
Elliot
J J
JJ
Carnes
D L
DL
Fox
W C
WC
Peña
L A
LA
Campion
S L
SL
Takahashi
K
K
Atkinson
B L
BL
Zamora
P O
PO
D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D001857:Bone Matrix / Q000187:drug effects; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins / Q000494:pharmacology*; D001861:Bone Regeneration / Q000187:drug effects; D002113:Calcification, Physiologic / Q000187:drug effects; D002460:Cell Line; D002828:Choristoma / Q000378:metabolism / Q000473:pathology; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D008297:Male; D051379:Mice; D010006:Osteoblasts / Q000187:drug effects; D010012:Osteogenesis / Q000187:drug effects*; D010455:Peptides / Q000494:pharmacology*; D010641:Phenotype; D039904:Pluripotent Stem Cells / Q000187:drug effects; D011817:Rabbits; D011859:Radiography; D051381:Rats; D011923:Rats, Nude; D016212:Transforming Growth Factor beta / Q000494:pharmacology*; D014457:Ulna / Q000000981:diagnostic imaging / Q000187:drug effects
C519235:B2A2-K-NS; C525718:BMP2 protein, human; C525719:Bmp2 protein, mouse; C525720:Bmp2 protein, rat; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins; D036341:Intercellular Signaling Peptides and Proteins; D010455:Peptides; D016212:Transforming Growth Factor beta; D000469:Alkaline Phosphatase