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Endochondral Ossification

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Daniel Glenday

Bone Development Endochondral Ossification Endochondral mesenchyme  cartilage  bone most skeletal elements 1. activation/migration of mesenchymal osteogenic cells 2. mesenchymal cells attach to ECM and proliferate 3. differentiation into cartilage; proliferation, hypertrophy, mineralization 4. angiogenesis, vascular invasion 5. bone differentiation 1. CONDENSATION condensation mesenchymal cells condense due to migration and proliferation Perichondrium = outer ring of condensation perichondrium Type IIb, IX, XI ECM = Type IIb, IX, XI collagens 2. CHONDROCYTE DIFFERENTIATION mesenchymal cells  chondrocytes ECM = Type X Type X collagen ECM calcifies  blood vessel invasion VEGF (mediated by VEGF) 3. OSTEOBLAST ARRIVAL osteoblasts are from mesenchymal precursors secrete OSTEOID along fresh matrix type I collagen Type I imprisoned osteoblasts = osteocytes regulate osteoblast and osteoclast activity osteoclasts – derived from hematopoetic stem cells monocyte precursors collect and fuse at sites of bone resorption involved in tunneling, formation of Haversion systems involved in replacing cartilage primary ossification centers – at diaphysis bone formation is complete at time of birth growth at epiphyses after birth Bone Development Membraneous Ossification mesenchyme  bone flat skull bones, clavicle, facial bones plate aggregations of trabeculae induced by brain, epithelium outward-directed growth (osteoblasts outside, -clasts inside) sutures/fontenelles – where plates fuse in skull; for flexibilityres/fontenelles premature fusion = Craniosynostosis Craniosynostosis EMBRYOLOGICAL ORIGINS AXIAL SKELETON entirely from somites/somitomeres (of paraxial mesoderm) somites sclerotome sclerotome undergoes epithelial  mesenchymal trans. surrounds spinal cord and notochord  ossifies SKULL Neurocranium (around brain): sclerotome + NCC sclerotome, NCC Viscerocranium (face): NCC LIMB from somatic (dorsal) lateral plate mesoderm lateral plate mesoderm Osteoblasts – from mesenchyme at perichondrium Osteoclasts – blood-borne (osteopetrosis cured by parabiosis, bone marrow transplant)steopetrosis Mutations causing osteopetrosis: FOS – TF necessary for osteoclast formation fos SRC – encodes a TK necessary for ruffled borders src Bone Development BONE DETERMINATION AND PATTERNING BMP – bone morphogenetic proteins: induce bone formation BMP (discovered by orthopedic surgeons) TGF-B related signaling molecules BMP-5 mutants  short-ear phenotype BMP-5,
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