The Indian hedgehog--PTHrP system in bone development.

Abstract

During embryonic development the bones of the vertebrate skeleton develop by two different mechanisms. Most of the bones of the skull are formed by intramembranous ossification in which mesenchymal cells directly differentiate into osteoblasts. The second mechanism, called endochondral ossification, is used to form the bones of the axial and appendicular skeleton as well as some of the facial bones. Endochondral ossification (Erlebacher et al. 1995; Hinchcliffe and Johnson 1980) starts with mesenchymal cells that aggregate and differentiate into chondrocytes, thus forming cartilage elements which serve as templates for the later bones. Cells in the middle of these cartilage elements start to differentiate into hypertrophic chondrocytes, a step that is necessary for the invasion of blood vessels and the subsequent replacement of cartilage by bone. The chondrocytes in the cartilage elements are surrounded by a thin layer of flattened cells, the perichondrium. In parallel with the differentiation of hypertrophic chondrocytes, the perichondrium flanking the differentiating and hypertrophic chondrocytes differentiates into an osteoblast-containing periosteum, which secretes a layer of primary bone, the bone collar. Signals from the perichondrium/periosteum are thought to interact with signals from the cartilage itself in correlating hypertrophic differentiation with the differentiation of the perichondrium into a periosteum. To understand the process of endochondral ossification it is necessary to identify the specific signals regulating the different steps in this process and to analyze their interactions.