Augmentation of osseous phenotypes in vivo with a synthetic peptide

• Published in: Journal of orthopaedic research 2007-04, Vol.25 (4), p.531-539
• Main Authors: Lin, Xinhua, Elliot, J.J., Carnes, D.L., Fox, W.C., Peña, L.A., Campion, S.L., Takahashi, K., Atkinson, B.L., Zamora, P.O.
• Format: Article
• Language: English
• Subjects: Alkaline Phosphatase - metabolism; Animals; BMP-2; bone; Bone Matrix - drug effects; Bone Morphogenetic Protein 2; Bone Morphogenetic Proteins - pharmacology; Bone Regeneration - drug effects; Calcification, Physiologic - drug effects; Cell Line; Choristoma - metabolism; Choristoma - pathology; enhancement; Humans; in vivo; Male; Mice; Osteoblasts - drug effects; Osteogenesis - drug effects; Peptides - pharmacology; Phenotype; Pluripotent Stem Cells - drug effects; Rabbits; Radiography; Rats; Rats, Nude; synthetic peptide; Transforming Growth Factor beta - pharmacology; Ulna - diagnostic imaging; Ulna - drug effects
• ISSN: 0736-0266; 1554-527X
• DOI: 10.1002/jor.20303

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. © 2006 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 25:531–539, 2007