Editing Endochondral ossification (section)

==Primary center of ossification==
[[File:41413 2018 21 Fig1 HTML.jpg|upright=1.5|thumb|A schematic for [[long bone]] endochondral ossification.]]
In developing bones, ossification commences within the primary ossification center located in the center of the [[diaphysis]] (bone shaft),<ref name="Elsevier" /> where the following changes occur:

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<li>The perichondrium surrounding the cartilage model transforms into the [[periosteum]]. During this transformation, special cells within the perichondrium switch gears. Instead of becoming cartilage cells ([[chondrocytes]]), they mature into bone-building [[osteoblasts]].<ref name="Elsevier" /> This newly formed bone can be called "periosteal bone" as it originates from the transformed periosteum. However, considering its developmental pathway, it could be classified as "intramembranous bone".<ref name="Paw" /></li>
<li>After the formation of the periosteum, chondrocytes in the primary center of ossification begin to grow ([[hypertrophy]]). They begin secreting:<ref name="Richard" /><ref name=Plastic>{{cite journal |last1=Chagin |first1=AS |last2=Chu |first2=TL |title=The Origin and Fate of Chondrocytes: Cell Plasticity in Physiological Setting. |journal=Current Osteoporosis Reports |date=December 2023 |volume=21 |issue=6 |pages=815–824 |doi=10.1007/s11914-023-00827-1 |pmid=37837512 |pmc=10724094}}</ref>{{bulleted list |[[Collagen]] type X, which causes stiffness and compression of the [[extracellular matrix]].| [[Matrix metalloproteinases]].| [[Vascular endothelial growth factor]] (VEGF), which controls forthcoming vascular invasion.|[[Alkaline phosphatase]], which causes calcification of the cartilage matrix. This calcification prevents passage of nutrients to chondrocytes leading to their death. }} 
<li>When chondrocytes die, matrix metalloproteinases result in catabolism of various components within the extracellular matrix and the physical boundaries between neighboring [[Lacuna (histology)|lacunae]] (the spaces housing chondrocytes) weaken. This can lead to the merging of these lacunae, creating larger empty spaces.<ref name="Paw" /><ref name="Jun" />
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<li>Blood vessels arising from the periosteum invade these empty spaces and mesenchymal stem cells migrate guided by penetrating blood vessels. Following the invading blood vessels, mesenchymal stem cells reach these empty spaces and undergo differentiation into osteoprogenitor cells. These progenitors further mature into osteoblasts, that deposit unmineralized bone matrix, termed osteoid. Mineralization subsequently follows leading to formation of bone trabeculae (Endochondral bone formation).<ref name="Plastic" />
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[[File:Hypertrophic Zone of Epiphyseal Plate.jpg|thumb|[[Light micrograph]] of undecalcified [[epiphyseal plate]] showing endochondral ossification: healthy [[chondrocyte]]s (top) become degenerating ones (bottom), characteristically displaying a calcified [[extracellular matrix]].]]