Endochondral ossification: how cartilage is converted into bone in the developing skeleton.
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 osteoclasts. This review, which places an emphasis on recent advances and current areas of debate, discusses the complex interactions between cell types and signalling pathways that govern endochondral ossification.
School of Veterinary Science, University of Melbourne, Parkville, Victoria 3010, Australia. ejmackie@unimelb.edu.au
E J
EJ
Mackie
Y A
YA
Ahmed
L
L
Tatarczuch
K-S
KS
Chen
M
M
Mirams
D001846:Bone Development / Q000502:physiology*; D019485:Bone Morphogenetic Proteins / Q000502:physiology; D002356:Cartilage / Q000166:cytology / Q000502:physiology*; D002454:Cell Differentiation / Q000502:physiology*; D019902:Chondrocytes / Q000166:cytology / Q000502:physiology*; D005346:Fibroblast Growth Factors / Q000502:physiology; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D008954:Models, Biological; D010281:Parathyroid Hormone / Q000502:physiology; D015398:Signal Transduction; D014157:Transcription Factors / Q000502:physiology; D042461:Vascular Endothelial Growth Factor A / Q000502:physiology
D019485:Bone Morphogenetic Proteins; D010281:Parathyroid Hormone; D014157:Transcription Factors; D042461:Vascular Endothelial Growth Factor A; D005346:Fibroblast Growth Factors