Fig 1.

Endochondral bone formation. Long bones are built up by endochondral mechanisms. In the beginning, mesenchymal cells form condensations. At the border of condensations, cells constitute the perichondrium (Pc), and into the inner condensations, cells differentiate into chondrocytes. Chondrocytes from the resting zone start to proliferate, thus generating columns of proliferating chondrocytes. The latter become hypertrophic and by their secretion of VEGF, attract blood vessels and undergo apoptosis, giving rise to a scaffold for osteoblasts accompanying the vascular ingrowth. In addition to VEGF, hypertrophic chondrocytes express Ihh, which regulates positively the expression of PTHrP by chondrocytes from the resting zone. However, PTHrP induces the proliferation of chondrocytes, inhibiting their capacity to become hypertrophic. Ihh-producing hypertrophic chondrocytes are generated when proliferating chondrocytes reach a location where PTHrP is insufficient. Their Ihh secretions also induce Runx2 expression from periosteal cells (Po) differentiating them into osteoblasts from bone collar. Osteoblasts and chondroblasts invading the growth plate through vessels forming primary spongiosa remodel bone to form trabeculation. Crucial proteins for growth plate development are noted according their expression area.