Bone development

The sequential cellular and molecular details of the initial embryonic formation of bone can be used to gain insight into the control of this process and subsequent bone physiology and repair. The functioning of osteogenic cells is governed by a complex balance between the intrinsic capacities of these cells in the context of extrinsic information and signalling. As with other mesenchymal tissues, the balance of intrinsic versus extrinsic capacities and influences is central to understanding both the sequence and consequence of bone development. It has been suggested that the cartilaginous model which forms at the centre of limbs is responsible for, and provides the scaffolding for, subsequent bone formation. Our recent studies of the embryonic chick tibia indicate that osteogenic progenitor cells are observed before the formation of the chondrogenic core. In particular, a layer of four to six cells, referred to as Stacked Cells, forms around a prechondrogenic core of undifferentiated cells. These osteoprogenitor cells give rise to all of the newly forming bone. Importantly, this newly forming bone arises outside and away from the chondrogenic core in a manner similar to the intramembranous bone formation seen in calvariae. Indeed, the cartilaginous core is replaced not by bone but by vascular and marrow tissues. The interplay between the osteogenic collar and the chondrogenic core provides an environment which stimulates the further differentiation of the cartilage core into hypertrophic cartilage and eventually renders this core replaceable by vascular and marrow tissue. There is an intimate relationship between the osteogenic cells and the vasculature which is obligatory for active bone formation. Bone formation in long bones, such as the tibia, as well as in the calvaria seems to proceed in a similar manner, with vascular tissue interaction being the most important aspect of successful osteogenesis, as opposed to the presence or interaction of cartilage. Our studies have focused on the development of long bones in aves, but detailed study of mouse and man indicates that many of the general features observed for birds apply to bone development in mammals. It is our current thesis that the general rules governing embryonic formation of long bones also apply to the formation of ectopic bone and are related to aspects of fracture repair.