Normal Skeleton- Vanguri

Question 1

What is CBFA1?

Answer 1

• Core Binding Factor Subunit
• Required for Differentiation of Mesenchymal Stem Cells into Osteoblasts.

Note: Mice with mutations in this show no bone formation.

Question 2

Aside from Bone formation, what do Osteoblasts do?

Answer 2

Regulate the function of Osteoclasts through binding of RANKL (on its own surface) and RANK (on Osteoclast surface).

Question 3

What Controls RANKL Expression?

Answer 3

• PTH Related Protein

- Serum Vitamin D3

Question 4

How do Osteocytes bind to surface of bone?

Answer 4

• Via integrins.

- They form resorption pits during active remodeling called Howship’s lacunae.

Question 5

Woven Bone

Answer 5

• Immature Bone (unmineralized) and weaker than Lamellar bone.
• Common in the developing Skeleton
• Disorganized matrix
• Seen under pathological condition in adults
• Around Fracture sites
• Bone tumors
• Paget’s Disease (rapid burn turnover)
• Hyperparathyroidism

Question 6

Lamellar Bone

Answer 6

• Mature bone
• Parallel arrangement of light and dark bands

Categorized according to location in bone:

• Cortical (compact) bone is tightly packed and arranged in perimeter of bones.
• Trabecular bone (Cancellous/Spongy) is on the inside of the bone.

Question 7

Cancellous Bone and Hematopoiesis

Answer 7

• Well perfused thus facilitates Hematopoiesis

- Plenty of space between trabeculae for marrow to reside.

Question 8

In bone development, Peripheral Mesenchymal cells give rise to?

Answer 8

• Blood vasculature

- Osteoblasts

Question 10

When does bone development take place?

Answer 10

Development of bone from a primitive cartilage matrix is termed Endochondral Ossification.

-Begins at Week 8.

Question 11

What are primary and secondary Spongiosa?

Answer 11

• Primary Spongiosum is the core of calcified cartilage and primitive bone during Endochondral ossification
• Osteoclasts remove the calcified cartilage and Osteoblasts fill it with Lamellar bone- this is Secondary Spongiosum.

Question 12

Skull Formation

Answer 12

-Undergoes Intramembranous Ossification.

Question 13

Discuss Primitive Mesenchymal Condensations and Defects

Answer 13

• Cartilage and bone develop from mesenchymal condensations. These condensations form the outline of the bone.
• Transcription factors guide development.
• Defects in the condensations lead to bone malformation.
• Defects in the RUNX2/CFAB1 TF lead to malformations.

Question 14

What is Achondroplasia?

Answer 14

• Autosomal Dominant mutation in Fibroblast Growth Factor Receptor 3 (FGFR3). Sometimes Sporadic.
• FGFR3 becomes constitutively active.
• Results in Cartilage growth Inhibition.
• Histo: Decreased Proliferative and Hypertrophic zones.

Question 15

What is Thanatophoric Dwarfism?

Answer 15

• Mutation in FGFR3 gene
• Lethal form of Dwarfism

-Results in shortened Thoracic height and death during infancy due to Respiratory Failure.

Question 16

What is Osteogenesis Imperfecta?

Answer 16

• Mutation in COL1A1 or COL1A2 (fatal) gene.
• Type I Collagen defect.
• Autosomal Dominant

Results in: BBB

• Brittle bones
• Blue Sclera
• Blown eardrums (hearing loss)

Note: Type I has normal life expectancy and Type II is fatal due to intrauterine fractures.

Question 17

What is Achondrogenesis?

Answer 17

• COL2 mutation

- Type II Collagen defect.

Question 18

What is Osteopetrosis?

Answer 18

-Defect in Osteoclast ability to resorb bone.

Results in:

• Thickened bones with bulbous ends (Erlenmeyer Flask sign)
• Increased bone density.
• Cranial nerve compression due to nearly absent foramina.

Question 18

What is the difference between Intermembranous and Enchondral bone formation?

Answer 18

• Intermembranous bone formation is when bone is formed directly from Mesenchymal cells.
• Enchondral bone formation is when bone is formed via a cartilage intermediary.