Osteoinduction: basic principles and developments

The term osteoinduction applies to the process by which osteogenesis is aroused. The process itself is a complex mechanism that induces, stimulates and regulates the production of calcified bone matrix. This phenomenon regularly takes place in any type of bone healing process. Osteoinduction provides the recruitment of immature cells and the stimulation of the mesenchymal stem cells along an osteoblastic pathway and leads these cells in the formation and apposition of new bone until healing. In the normal healing process osteoinduction plays perhaps the most critical role in effecting bone repair. Osteoinduction and the intrinsic osteoinductive properties of native bone were emphasized by the historical works of Marshall Urist in 1965. He demonstrated that demineralized bone matrix (DBM) may induce a local inflammatory response, which leads to formation of bone matrix in the muscle pouch of rats. From these experiments the concept of osteoinduction has grown and has been refined over the years to understand the different steps and the different actors playing their roles. Urist [1] defined this discovery of the bone induction principle few years later and he and his co-workers continued the studies until this capacity was attributed to some polypeptides named bone morphogenetic proteins (BMPs). Only 20 years later the genetic sequences of the BMPs were identified and classified with the identification of a number of different BMPs whose precise role in the osteoinduction process is still extensively studied and not well defined. But experimental and preclinical studies have shown also that the BMPs are not playing alone on this stage. Many proteins secreted by the cells are implied in the process of healing and new bone formation; to these factors has been generically assigned the term "growth factors" and an increasing number of these have been identified and used in experimental studies. The more debated are the transforming growth factor-β(TGF-β), the fibroblast growth factor (FGF), the insulin-like growth factor (IGF) and the platelet-derived growth factors (PDGF). Obviously these are only some of the variety of factors that participate in a normal healing process, but are those that seem more implied with bone apposition. More recently osteoinduction has seen the proposal of gene therapy for curing bone diseases such as osteogenesis imperfecta and osteopetrosis, but these experiments are still on the starting blocks and will only be presented here.