Bone morphogenetic proteins: from basic science to clinical applications.
J Bone Joint Surg Am. 2001;83-A Suppl 1(Pt 1):S1-6. Review

The role of bone morphogenetic proteins (BMPs) in bone formation during development and in fracture-healing is now well established. In experimental animals, BMPs elicit bone formation in ectopic sites and healing of critical-sized segmental bone defects. Many of the studies on the capacity of BMPs to elicit the healing of segmental bone defects have been carried out in orthopaedic research laboratories and are familiar to orthopaedic surgeons.

However, until recently little was known about the cellular and molecular mechanisms by which BMPs elicit bone formation. In a series of stunning studies over the last several years, molecular cell biologists working intensively in several laboratories have elucidated some of these mechanisms. When BMPs bind to their cell surface receptors on mesenchymal cell, a BMP signaling cascade is activated. Signals are sent via specific proteins to the cell nucleus. This results in the expression of genes that lead to the synthesis of macromolecules involved in cartilage and bone formation, and the mesenchymal cell becomes a chondrocyte or an osteoblast.

The development of knowledge in this area of BMP signal transduction during the last several years has been phenomenal and has provided a substantial amount of new information that is clear-cut, specific, and useful. Some of this new information may be of clinical relevance because it suggests potential therapeutic approaches to enhance or suppress new bone formation. Several of the studies on the mechanisms of BMP signal transduction presented at the International Conference on Bone Morphogenetic Proteins (held in Lake Tahoe, California, June 7 through 11, 2000) have been included in this supplement. In each article, the authors have included in the introductory section a lucid summary of the development of knowledge in a particular area.