[Bone morphogenetic protein (BMP): from basic studies to clinical approaches].

The bone morphogenetic proteins (BMPs) are members of the TGF-beta gene superfamily, a large family of secreted signaling molecules. When implanted locally to animals with appropriate carriers, recombinant human BMP-2 (rhBMP-2) and some other members of BMPs reproduced very potent, ectopic bone forming activity. In vitro, rhBMP-2 is shown to induce differentiation of mesenchymal stem cells into osteoblast and chondroblast cells and to prevent the former cells from differentiating into cell types other than the latter cells. Several BMP (IA, IB and II) receptors, which belong to the TGF-beta receptor family of serine/threonine kinases, have also been cloned and characterized. The intracellular signal transduction and transcriptional factors associating with BMP receptors are also being investigated. For clinical applications, we have developed suitable carriers for rhBMP-2, which are biocompatible, biodegradable and non-immunogenic. We have also shown that rhBMP-2, combined with such carriers, induces significant bone formation in various kinds of bone defect models that mirror clinical applications in rodents and larger animals, including non-human primates. These preclinical studies have proved that the bone induced by rhBMP-2 seemed to behave as morphologically and mechanically normal. Clinical trials are underway to determine its usefulness in orthopedic and oral and maxillofacial fields.