BMP-8, also known as osteogenic protein 2 (OP-2), was first isolated from a hippocampal library in a screen to identify relatives of BMP-7 (OP-1) (1). BMPs are a family of structurally and functionally related proteins and represent a subfamily of the transforming growth factor beta (TGF-beta ) superfamily. BMPs were originally identified as protein regulators of cartilage and bone formation. They have since been shown to be involved in embryogenesis and morphogenesis of various tissues and organs (2). BMPs play roles in regulating growth, differentiation, chemotaxis, and apoptosis of various cell types, including mesenchymal, epithelial, hematopoetic, and neuronal cells.
There exist two highly related and closely linked genes, designated BMP-8a and -8b in mice and humans. For humans, the protein products of these two genes share 98% amino acid (aa) sequence identity in their pro- and mature regions. However in the mouse, the two proteins share 89% and 76% aa sequence homology in their pro- and mature regions, respectively (3). Mature human BMP-8a shares 91% and 70% aa sequence identity with mouse BMP-8a and -8b, respectively. Human BMP-8a is synthesized as a large precursor protein that is cleaved at a dibasic cleavage site (RTPR) between aa residues 263 and 264 to release a 139 aa carboxy-terminal domain. Expression patterns of the BMP-8 genes indicate that they regulate aspects of cell proliferation and/or differentiation during spermatogenesis and formation of the placenta (3). BMP-8 is also highly expressed in osteosarcomas (4).
