title: B2A as a positive BMP receptor modulator.
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.
authors.affiliation: BioSurface Engineering Technologies, Inc., Rockville, MD 20850, USA. xlin@biosetinc.com
authors.forename: Xinhua
authors.initials: X
authors.lastname: Lin
authors.forename: Henry
authors.initials: H
authors.lastname: Guo
authors.forename: Kazuyuki
authors.initials: K
authors.lastname: Takahashi
authors.forename: Yi
authors.initials: Y
authors.lastname: Liu
authors.forename: Paul O
authors.initials: PO
authors.lastname: Zamora
mesh_terms: D000818:Animals; D055396:Bone Morphogenetic Protein 2 / Q000378:metabolism*; D052004:Bone Morphogenetic Protein Receptors / Q000378:metabolism*; D002454:Cell Differentiation; D002460:Cell Line; D005786:Gene Expression Regulation; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D051379:Mice; D010006:Osteoblasts / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D010455:Peptides / Q000235:genetics / Q000378:metabolism*
chemical_list: C519235:B2A2-K-NS; D055396:Bone Morphogenetic Protein 2; D036341:Intercellular Signaling Peptides and Proteins; D010455:Peptides; D052004:Bone Morphogenetic Protein Receptors