Recombinant Human BMP-2/BMP-7 Heterodimer Protein

Human BMP-7, also known as osteogenic protein 1 (OP-1), and BMP-2 are members of the BMP subgroup of the TGF-beta superfamily and signal through heterodimeric complexes composed of type I and type II BMP receptors. BMP-2 and BMP-7 influence a variety of morphogenic processes, particularly during skeletal and renal development (1 - 3). The human BMP-2 cDNA encodes a 396 amino acid (aa) precursor that contains a 23 aa signal sequence, a 259 propeptide, and a 114 aa mature protein (4). The human BMP-7 cDNA encodes a 431 aa precursor that contains a 29 aa signal sequence, a 263 aa propeptide, and a 139 aa mature protein (5). BMP propeptides are removed by proteolysis, enabling mature BMPs to form active disulfide linked homodimers or heterodimers (1). Human and mouse BMP-2 and BMP-7 are 100% and 98% identical, respectively, at the amino acid level. Human BMP-2 shares 85% aa sequence identity with human BMP-4 and less than 51% aa sequence identity with other BMPs. Human BMP-7 shares approximately 60% - 70% aa sequence identity with BMP-5, -6, and -8, and less than 50% aa sequence identity with other BMPs. BMP-2 and BMP-7 are co-expressed in some embryonic tissues (6, 7) and associate into a functional 38 kDa osteogenic dimer (8). In in vitro osteoblast differentiation assays and in vivo bone formation models, a BMP-2/BMP-7 heterodimer is significantly more potent than either homodimer (9 - 12). Considering that BMP-2 preferentially binds BMPRIA/ALK-3 and BMPRIB/ALK-6, while BMP-7 is selective for ALK-2, the observed increase in heterodimer activity may be due to the triggering of additional receptor subtypes.