[Differentiation of osteogenetic cells: systems and regulators]

Abstract

Bone formation comprises a complex but ordered sequence of events, beginning with the proliferation of chondrogenic and osteogenic precursor cells followed by their subsequent differentiation, ultimately leading to extracellular matrix maturation and mineralisation. Several models have been established which recreate discrete elements of this network. Factors induce ectopic bone formation, when implanted into muscle pouches, have been characterized as members of the TGF-beta-superfamily. Detailed information about the course of OB-differentiation has been obtained from an in vitro model system. The process of mineralisation was found to consist of three distinct time periods: a proliferative phase, a period of extracellular matrix maturation and mineralisation. The development of each states depends on each other. This model is not as complex as the whole organ and cannot of course lead to any conclusion about the kinetic differentiation path of a cell in its normal spatial environment. Different organ culture systems are described and through the application of sensitive methods the differentiation can be studied in the normal spatial environment. The cascade of events in the differentiation process must be strictly regulated. Hormones and growth factors in many cases show a bone-forming and/or bone-resorbing action. The effects of the classical calcium regulating hormones Vitamin D and PTH on OB-differentiation are reviewed. A large number of growth factors have been shown to effect OB. Growth factors, that have been isolated from the bone matrix are of particular interest to bone formation.