Molecular control of endochondral ossification. Transcription factors (Cbfa1 and others) promote the differentiation of the type II collagen–producing cells present in the skeletal mesenchymal condensations into Ihh-secreting hypertrophic chondrocytes. Ihh then acts both on the cells of the perichondrium and on the cells of the bone collar. In the perichondrium, Ihh favors the production of PTHrP, which in turn inhibits chondrocyte hypertrophy. In the bone collar, Ihh induces the expression of Cbfa1, which triggers the osteoblastic differentiation of these cells. Hypertrophic chondrocytes also secrete VEGF, which promotes vascular invasion of the skeletal structure. Blood vessels reach the hypertrophic area, chondroclast/osteoclasts and resorb the ossified cartilaginous matrix. Osteoblasts derived from the bone collar replace this matrix with a bone matrix rich in type I collagen.