Endochondral ossification is the process by which the embryonic cartilaginous model of most bones contributes to longitudinal growth and is gradually replaced by bone. During endochondral ossification, chondrocytes proliferate, undergo hypertrophy and die; the cartilage extracellular matrix they construct is then invaded by blood vessels, osteoclasts, bone marrow cells and osteoblasts, the last of which deposit bone on remnants of cartilage matrix. The sequential changes in chondrocyte behaviour are tightly regulated by both systemic factors and locally secreted factors, which act on receptors to effect intracellular signalling and activation of chondrocyte-selective transcription factors. Systemic factors that regulate the behaviour of chondrocytes in growth cartilage include growth hormone and thyroid hormone, and the local secreted factors include Indian hedgehog, parathyroid hormone-related peptide, fibroblast growth factors and components of the cartilage extracellular matrix. Transcription factors that play critical roles in regulation of chondrocyte gene expression under the control of these extracellular factors include Runx2, Sox9 and MEF2C. The invasion of cartilage matrix by the ossification front is dependent on its resorption by members of the matrix metalloproteinase family, as well as the presence of blood vessels and bone-resorbing osteoclast (Mackie et al.) This pathway was inferred from Homo sapiens pathway [http://www.wikipathways.org/index.php?title=Pathway:WP474&oldid=29737 WP474(r29737)] with a 94% conversion rate. e1e fee T4 PMID: 17097081 Taken as homologue to mouse Cathepsin L (Ctsl) Taken as human homologue of mouse Cst10 PMID: 13679380 Direction of effect unclear 18374667 PubMed A microarray approach for comparative expression profiling of the discrete maturation zones of mouse growth plate cartilage. Biochim Biophys Acta 2008 Belluoccio D Bernardo BC Rowley L Bateman JF 17659995 PubMed Endochondral ossification: how cartilage is converted into bone in the developing skeleton. Int J Biochem Cell Biol 2008 Mackie EJ Ahmed YA Tatarczuch L Chen KS Mirams M regulatory pathway PW:0000004 Pathway Ontology