During endochondral bone formation, mesenchymal condensations, chondrocyte differentiation and proliferation, termination of proliferation, hypertrophic differentiation, and replacement by bone occur sequentially. This sequence is spatially represented by the structure of the growth plate of the embryo, and reflects the evolution of bone. Endochondral bone formation is mainly regulated by the interactions of chondrocytes and osteoblasts; a variety of signals are implicated in this regulation. The roles of factors regulating chondrocyte proliferation and hypertrophy including the Sox trio, PTH related peptide (PTHrP), Indian hedgehog (Ihh), the runt-related transcription factor (Runx) family, fibroblast growth factor receptor 3 (FGFR3) and bone morphogenetic protein (BMP) and other factors including hypoxia-inducible factor 1alpha (HIF-1alpha) and vascular endothelial growth factor (VEGF) will be discussed.

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