Description
Bone morphogenetic protein 7 (BMP7), also known as osteogenic protein 1 (OP1), is a widely expressed TGF super family member with important functions during embryogenesis, in the adult, and in disease (1, 2). Mouse BMP7 is synthesized with a 29 amino acid (aa) signal sequence, a 262 aa propeptide, and a 139 aa growth fact or domain (3). The growth factor domain of mouse BMP7 shares 98% and 100% aa sequence identity with human and rat BMP7, respectively. The BMP7 propeptide is cleaved intracellularly but remains in association with the growth factor domain. BMP7 is subsequently secreted as a tetramer that consists of two propeptides and two disulfidelinked growth factor domains (4, 5). Mature BMP7 can also form disulfidelinked heterodimers with BMP2 or BMP4, complexes that show increased potency and range of activity compared to BMP7 homodimers (68). The presence of the propeptides in the BMP7 tetramer does not diminish the bioactivity of the growth factor domains (5). Secreted BMP7 is immobilized in the extracellular matrix as a result of interactions between the propeptide and matrix fibrillin (4). BMP7 exerts its biological effects through the type 2 receptors Activin RIIA, Activin RIIB, and BMPRI I and the t ype 1 receptors Activin RIA, BMPRIA, and BMPRIB (2, 5). BMP7 plays a role in a variety of organ systems. It promotes new bone formation and nephron development (9, 10), inhibits the branching of prostate epithelium (11), and antagonizes epithelialmesenchymal transition (EMT) (1214). In pathological conditions, BMP7 inhibits tumor growth and metastasis (13), ameliorates fibrotic damage in nephritis (12), and promotes neuroregeneration following brain ischemia (15)