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Abstract
B2A (B2A2-K-NS) is a synthetic multi-domain peptide that in vitro augments bone morphogenetic protein (BMP)-2-induced cell responsiveness and osteodifferentiation. Augmentation of endogenous BMP-2 is thought to ultimately improve bone repair, and has led to clinical evaluation of B2A in orthopedic applications. In this study, we show that B2A binds to BMP receptor (BMPR)-IB, BMPR-II, and BMPR-IA. B2A reduces the EC50 of rh-BMP-2, thus shifting the response curve to the left. B2A enhances the osteogenic activity of BMP-2, but not growth and differentiation factor-5, BMP-7, or BMP-9, indicating its action is highly BMP-2 selective. Additionally, B2A did not augment Wnt-3a- and retinoic acid-induced differentiation. All three functional domains (receptor-binding domain, hydrophobic-linker domain, heparin-binding domain) of B2A are required for optimal bioactivity. Collectively, the results suggest that B2A, via its unique sequence, acts in a manner consistent with a positive receptor modulator to selectively enhance BMP-2 osteodifferentiation, and yet in the absence of BMP-2, B2A is without cooperative effect.
Acknowledgements
Parts of this work were conducted under contract with the University of Maryland, Baltimore, MD; and SA Biosciences Corporation, Frederick, MD.
Declaration of interest: Financial support of this work was provided by BioSET, Inc. All the authors are employees of BioSET, Inc. and either own stock/stock options or have other equity in BioSET, Inc. The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.