Background:

BMPs (Bone Morphogenetic Proteins) belong to the TGF-beta superfamily of structurally related signaling proteins. BMP-2 is a potent osteoinductive cytokine, capable of inducing bone and cartilage formation in association with osteoconductive carriers such as collagen and synthetic hydroxyapatite. In addition to its osteogenic activity, BMP-2 plays an important role in cardiac morphogenesis. The functional form of BMP-2 is a 26 kDa protein composed of two identical 114 amino acid polypeptide chains linked by a single disulfide bond. Each BMP-2 monomer is expressed as the C-terminal part of a precursor polypeptide, which also contains a 23 amino acid signal sequence for secretion, and a 259 amino acid propeptide. After dimerization of this precursor, the covalent bonds between the propeptide (which is also a disulfide-linked homodimer) and the mature BMP-2 ligand are cleaved by a furin-type protease.

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.

Bone morphogenetic protein 2 is shown to stimulate the production of bone and recombinant human protein (rhBMP-2) and is currently available for orthopaedic usage in the United States. Implantation of BMP-2 in a collagen sponge induces new bone formation and can be used for the treatment of bony defects, delayed union, and non-union. Bone morphogenetic protein 2 has also found its way into the field of Dentistry. Oral Surgery and Implant Dentistry in particular have benefited dramatically from commercially available BMP-2.