Bi117 Bone and Cartilage (2/27/14)

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What does alcian blue stain?

Cartilage

What does alizarin red stain

Bone

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

Intramembranous ossification

Directly converts mesenchymal cells into bone

Endochondral ossification

Mesenchymal cells differentiate into cartilage first and later replaced by bone

Sclerotome becomes

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

Sox9

Factor that initiates osteogenesis

Runx2

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

Chondrocytes proliferate.
Then, they stop dividing and increase volume aka hypertrophy. This plus runx2 is necessary and sufficient for development of osteoblasts

HDAC4 is...

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...

Premature ossification

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

Growth zone

Epiphyseal plates

Greatest contribution to growth rate in mammals

Massive enlargement of hypertrophic chondrocytes

Role of fgf signaling

Fgfr3 expressed by proliferating chondrocytes

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