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Bi117 Bone and Cartilage (2/27/14)
What does alcian blue stain?
What does alizarin red stain
3 distinct lineages that generate the skeleton
Paraxial mesoderm, cranial neural crest, lateral plate mesoderm
Paraxial mesoderm gives rise to
Axial skeleton, craniofacial bones
Cranial neural crest gives rise to
Craniofacial bones and cartilage
Lateral plate mesoderm gives rise to
Appendicular (limb) skeleton
2 major modes of bone formation
Intramembranous and endochondral ossification
Directly converts mesenchymal cells into bone
Mesenchymal cells differentiate into cartilage first and later replaced by bone
Mesenchymal... Bone and cartilage and muscle of the axial skeleton (vertebrae and ribs)
Endochondral ossification involved in forming
Vertebrae, ribs, limbs
Two pathways for undifferentiated mesenchyme
Chondrogenesis or osteogenesis
Factor that initiates chondrogenesis
Factor that initiates osteogenesis
Stages of endochondral ossification
Commitment, compaction, proliferation, growth, chondrocyte death and bone cell generation
1-2 commitment and compaction
Shh induces sclerotome to express pax1 so that cartilage specified, bmps induce expression of adhesion molecules and sox9, sox9 induces collagen formation
3-4 Proliferation and growth
Then, they stop dividing and increase volume aka hypertrophy. This plus runx2 is necessary and sufficient for development of osteoblasts
A histone deacetylase. Expressed solely in prehypertrophic chondrocytes. Inhibits runx2 so that hypertrophy does not occur prematurely
If HDAC4 is overexpressed...
It inhibits runx2, so no bone is formed
If HDAC4 knocked out...
Chondrocytes also alter matrix and secrete
Vegf for angiogenesis, ihh to activate runx2
Hypertrophic cartilage is important in regulating...
Final size of long bone, swelling determine elongation rate
5 Chondrocyte death and bone cell generation
Hypertrophic chondrocytes undergo apoptosis, replaced by bone, blood vessels invade cartilage model.
Osteoblasts form bone matrix and become osteocytes.
How do osteoblasts become osteocytes?
Wnt activates osterix
Greatest contribution to growth rate in mammals
Massive enlargement of hypertrophic chondrocytes
Role of fgf signaling
Fgfr3 expressed by proliferating chondrocytes