Recombinant Human BMP-9 Protein, CF

Human BMP-9, also known as growth and differentiation factor 2 (GDF-2), is a member of the BMP subgroup of the TGF-beta superfamily proteins that signal through heterodimeric complexes composed of type I and type II BMP receptors. BMP-9 regulates the development and function of a variety of embryonal and adult tissues (1, 2). The human BMP-9 cDNA encodes a 429 amino acid (aa) precursor that includes a 22 aa signal sequence, a 298 aa propeptide, and a 111 aa mature protein (3). Unlike with other BMP family proteins, the propeptide does not interfere with the biological activity of BMP-9 and remains associated with the mature peptide after proteolytic cleavage (4). Human and mouse BMP-9 share 96% aa sequence identity. Within the mature protein, human BMP-9 shares 64% aa sequence identity with human BMP-10 and less than 50% aa sequence identity with other BMPs. BMP-9 is expressed by non-parenchymal cells in the liver, (5, 6) where it promotes lipid metabolism and inhibits glucose production (7). BMP-9 exerts a prolonged hypoglycemic effect which may be due to an enhancement of insulin release (7). BMP-9 interacts with a high affinity specific heteromeric receptor expressed on liver endothelial cells that has been identified as ALK-1 (4 - 6). In the embryonal CNS, BMP-9 functions in the development and maintenance of the cholinergic neuronal phenotype (8 - 10). BMP-9 also induces the differentiation of mesenchymal stem cells into the chondrogenic lineage (11, 12). At low concentrations, BMP-9 is a proliferative factor for hematopoietic progenitor cells, but at higher concentrations, it enhances TGF-beta 1 production and inhibits hematopoietic progenitor colony formation (13).