Induction and maintenance of new bone formation by growth and differentiation factors

The cell biology of bone formation can be better understood by dissecting the complex multistep process into individual steps. It is well known that demineralized matrix has the potential to initiate new bone formation locally at a heterotopic site of implantation. The sequential development of bone in response to bone matrix is reminiscent of the cellular lineages in the epiphyseal growth plate. The developmental cascade has permitted the operational distinction of the major phases of new bone formation such as: migration of progenitor cells; mitosis of mesenchymal stem cells; differentiation to cartilage and bone; mineralization and remodelling; and finally hematopoietic marrow differentiation. Thus the initiation of bone formation can be investigated as opposed to maintenance of already formed bone as in the orthotopic sites. Recent work has resulted in the identification and isolation of osteogenin, a bone-inductive protein. The newly formed bone is then maintained by a variety of polypeptide growth factors which have a regulatory role. The local action of initiation and maintenance factors is further modulated in a collaborative manner by systemic factors such as hormones and nutrition and the extracellular matrix.