Cellular and molecular events during embryonic bone development.

The cellular events underlying the processes of bone maintenance, remodeling, and repair have their basis in the embryonic production of bone. Although it has been suggested that the cartilaginous model which resides in the center of developing limbs provides the scaffolding for new bone formation, our detailed morphological and histochemical studies indicate otherwise. In particular, there exists a layer of four to six cells, referred to as Stacked Cells, which surrounds a prechondrogenic core of undifferentiated cells in the limb. These Stacked Cells give rise to the lineage of osteogenic cells responsible for the formation of all structural bone. This bone is fabricated outside of the cartilage core, and the core is not replaced by bone, but rather, is replaced by marrow and vascular elements. Several generalizations arise from analysis of the cellular and molecular events of embryonic osteogenesis, and they are as follows: 1) osteogenesis and chondrogenesis are independent events which are programmed early in development, 2) bone formation is a vascular driven phenomenon which is characterized by the directional nature of osteoid secretion, and 3) the fundamental events of bone formation are consistent in chick, rat, and human long bones.