BMP-7

Bone morphogenetic protein 7 (BMP-7), also known as osteogenic protein 1 (OP1), is a widely expressed TGFβ superfamily member with important functions during embryogenesis, in the adult, and in disease (1,2) . Human BMP-7 is synthesized with a 29 amino acid (aa) signal sequence, a 263 aa propeptide, and a 139 aa growth factor domain (3) . The growth factor domain of human BMP-7 shares 98% aa sequence identity with mouse and rat BMP-7. The BMP-7 propeptide is cleaved intracellularly but often remains associated with the mature C-terminus. Based on in vivo and in vitro studies, BMP-7 has the potential to be secreted as a disulfide-linked mature homodimer, or particularly as a heteromeric complex that consists of two propeptides noncovalently associated with a mature disulfide linked homodimer (5,6) . The presence of the propeptides in BMP-7 appears to stabilize the molecule and provide a docking mechanism for extracellular storage on molecules such as fibrillin1 and 2 (5,6) . The propeptides themselves do not impart latency to the complex. BMP-7 binding to type II receptors rapidly displaces the prodomain: mature molecule interaction and has no effect on activity. But it is suggested that immobilized BMP-7 (via prodomain:fibrillin) is inactive, allowing for possible long term storage of the molecule (6) . BMP-7 interacts with the type 2 receptors Activin RIIA, Activin RIIB, and BMPRII and the type 1 receptors Activin RIA, BMPRIA, and BMPRIB (2,6) . BMP-7 may also be processed into a disulfide-linked heterodimer with either BMP-2 or BMP-4. Such complexes may show increased potency and range of activity compared to BMP7 homodimers (7-9) . BMP-7 plays a role in a variety of organ systems. It promotes new bone formation and nephron development (10,11), inhibits the branching of prostate epithelium (12), and antagonizes epithelial mesenchymal transition (EMT) (13-15) . In pathological conditions, BMP-7 inhibits tumor growth and metastasis (14), ameliorates fibrotic damage in nephritis (13), and promotes neuro regeneration following brain ischemia (16) .