BIOL130 Lecture Notes - Bone Morphogenetic Protein 4, Achondroplasia, Fibroblast Growth Factor Receptor

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28 Jan 2013
Department
Course
Bone Development
Endochondral Ossification
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
mesenchymal cells condense due to migration and
proliferation
Perichondrium = outer ring of condensation
ECM = Type IIb, IX, XI collagens
2. CHONDROCYTE DIFFERENTIATION
mesenchymal cells chondrocytes
ECM = Type X
ECM calcifies blood vessel invasion
(mediated by VEGF)
3. OSTEOBLAST ARRIVAL
osteoblasts are from mesenchymal precursors
secrete OSTEOID along fresh matrix
type I collagen
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
Endochondral
condensation
perichondrium
Type IIb, IX, XI
Type X collagen
VEGF
Type I
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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 flexibility
premature fusion = Craniosynostosis
EMBRYOLOGICAL ORIGINS
AXIAL SKELETON
entirely from somites/somitomeres (of paraxial mesoderm)
sclerotome undergoes epithelial mesenchymal trans.
surrounds spinal cord and notochord ossifies
SKULL
Neurocranium (around brain): sclerotome + NCC
Viscerocranium (face): NCC
LIMB
from somatic (dorsal) lateral plate mesoderm
Osteoblasts – from mesenchyme at perichondrium
Osteoclasts – blood-borne
(osteopetrosis cured by parabiosis, bone marrow transplant)
Mutations causing osteopetrosis:
FOS – TF necessary for osteoclast formation
SRC – encodes a TK necessary for ruffled borders
sutures/fontenelles
Craniosynostosis
somites
sclerotome
sclerotome, NCC
lateral plate
mesoderm
osteopetrosis
fos
src
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