Mackie E J, Ahmed Y A, Tatarczuch L, Chen K-S, Mirams M
School of Veterinary Science, University of Melbourne, Parkville, Victoria 3010, Australia.
Int J Biochem Cell Biol. 2008;40(1):46-62. doi: 10.1016/j.biocel.2007.06.009. Epub 2007 Jun 29.
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.
软骨内成骨是大多数骨骼的胚胎软骨模型促进纵向生长并逐渐被骨替代的过程。在软骨内成骨过程中，软骨细胞增殖、肥大并死亡；它们构建的软骨细胞外基质随后被血管、破骨细胞、骨髓细胞和成骨细胞侵入，其中成骨细胞在软骨基质残余物上沉积骨。软骨细胞行为的顺序变化受到全身因素和局部分泌因子的严格调控，这些因子作用于受体以影响细胞内信号传导并激活软骨细胞选择性转录因子。调节生长软骨中软骨细胞行为的全身因素包括生长激素和甲状腺激素，局部分泌因子包括印度刺猬因子、甲状旁腺激素相关肽、成纤维细胞生长因子和软骨细胞外基质成分。在这些细胞外因子控制下，在软骨细胞基因表达调节中起关键作用的转录因子包括Runx2、Sox9和MEF2C。骨化前沿对软骨基质的侵入取决于基质金属蛋白酶家族成员对其的吸收，以及血管和骨吸收破骨细胞的存在。本综述着重于近期进展和当前的争议领域，讨论了控制软骨内成骨的细胞类型和信号通路之间的复杂相互作用。
