B2A as a positive BMP receptor modulator
| Autor: | Xinhua Lin, Henry Guo, Yi Liu, Paul O. Zamora, Kazuyuki Takahashi |
|---|---|
| Rok vydání: | 2012 |
| Předmět: |
medicine.medical_specialty
animal structures Cellular differentiation Clinical Biochemistry Cell Bone Morphogenetic Protein 2 Endogeny Biology Bone morphogenetic protein Cell Line Mice Endocrinology Internal medicine medicine Animals Humans Receptor Receptor modulator Regulation of gene expression Osteoblasts Cell Differentiation Bone Morphogenetic Protein Receptors Cell Biology BMPR2 Cell biology medicine.anatomical_structure Gene Expression Regulation embryonic structures Intercellular Signaling Peptides and Proteins Peptides |
| Zdroj: | Growth Factors. 30:149-157 |
| ISSN: | 1029-2292 0897-7194 |
| DOI: | 10.3109/08977194.2012.671310 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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