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Open Access 01-12-2009 | Research

Biological activity of a genetically modified BMP-2 variant with inhibitory activity

Authors: Uwe Klammert, Joachim Nickel, Kristian Würzler, Christoph Klingelhöffer, Walter Sebald, Alexander C Kübler, Tobias Reuther

Published in: Head & Face Medicine | Issue 1/2009

Abstract

Background

Alterations of the binding epitopes of bone morphogenetic protein-2 (BMP-2) lead to a modified interaction with the ectodomains of BMP receptors. In the present study the biological effect of a BMP-2 double mutant with antagonistic activity was evaluated in vivo.

Methods

Equine-derived collagenous carriers were loaded with recombinant human BMP-2 (rhBMP-2) in a well-known dose to provide an osteoinductive stimulus. The study was performed in a split animal design: carriers only coupled with rhBMP-2 (control) were implanted into prepared cavities of lower limb muscle of rats, specimens coupled with rhBMP-2 as well as BMP-2 double mutant were placed into the opposite limb in the same way. After 28 days the carriers were explanted, measured radiographically and characterized histologically.

Results

As expected, the BMP-2 loaded implants showed a typical heterotopic bone formation. The specimens coupled with both proteins showed a significant decreased bone formation in a dose dependent manner.

Conclusion

The antagonistic effect of a specific BMP-2 double mutant could be demonstrated in vivo. The dose dependent influence on heterotopic bone formation by preventing rhBMP-2 induced osteoinduction suggests a competitive receptor antagonism.

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Title: Biological activity of a genetically modified BMP-2 variant with inhibitory activity
Authors: Uwe Klammert
Joachim Nickel
Kristian Würzler
Christoph Klingelhöffer
Walter Sebald
Alexander C Kübler
Tobias Reuther
Publication date: 01-12-2009
Publisher: BioMed Central
Published in: Head & Face Medicine / Issue 1/2009
Electronic ISSN: 1746-160X
DOI: https://doi.org/10.1186/1746-160X-5-6

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Biological activity of a genetically modified BMP-2 variant with inhibitory activity

Abstract

Background

Methods

Results

Conclusion

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods

Results

Conclusion

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