Biology of Skeletal Tissue

Question 1

Cartilage

Answer 1

Derived from mesenchymal progenitors
Avascular
Resists tension and compression
Template to bone formation

Question 2

Types of Cartilage Growth

Answer 2

Appositional and Interstitial

Question 3

Appositional Growth

Answer 3

Perichondrial progenitor cells differentiate into chondroblasts

Question 4

Interstitial Growth

Answer 4

Chondrocytes divide in lacuna and synthesize matrix, giving rise to iosgenous groups

Question 5

Hyaline Cartilage

Answer 5

Articular surfaces of the joints, fetal tissue, respiratory system
Cushions
Chondrocytes are found in lacunae
Covered by perichondrium

Question 6

Elastic Cartilage

Answer 6

Found in External ear and auditory canal
Flexible
Elastic fibers

Question 7

Fibrocartilage

Answer 7

Attachement of tendons and intervertebral discs
Resists deformation
Chondrocytes in rows made up of type I collagen fibers
NO Perichondrium

Question 8

Chondrocyte Differentiation

Answer 8

Derived from mesenchymal cells
BMP –> Sox9 –> Sox5,6 –> Col2A1/ Aggrecan/ Link Protein
Sox9 tells mesenchymal cells to become chondroblasts
Sox 5,6 tells chondroblasts to become chondrocytes

Question 9

Periosteum

Answer 9

Fibrous Layer

Osteogenic Layer

Question 10

Endosteum

Answer 10

Bone lining cells

Contains osteoclasts

Question 11

Compact Bone

Answer 11

Cortical Bone

Perimeter of the bone

Question 12

Trabecular

Answer 12

Cancellous/ Spongy bone

Honeycomb like structure

Question 13

Osteoblasts

Answer 13

Produce Osteoid and subsequent mineralization
Support osteoclast development
2 months

Question 14

Bone Mineralization

Answer 14

Hydroxyapatite important bone mineral

Question 15

Regulation of Bone Mineralization

Answer 15

PPi inhibits bone mineralization
Extracellular PPi levels increased by NPP1 and ANK
NPPI transforms ATP to PPi
ANK is channel for PPi
PPi cleaved by TNAP (inhibits mineralization)

Question 16

Osteoblast Differentiation

Answer 16

Mesenchymal Cells > Pre OB > Immature OB > OB
Osteoblasts (OB) can become osteocytes or bone lining cells
Mesenchymal cells diff into pre OB by BMP –> Runx2

Question 17

RunX2

Answer 17

Transcription factor expressed in osteoblasts

Master regulator of osteoblast differentiation

Question 18

SOST (Sclerostin)

Answer 18

Produced by osteocytes and inhibits Wnt signaling

Inhibiting Wnt signaling inhibits osteoblast differentiation via BMP inhibition

Question 19

Effects on Inhibiting SOST

Answer 19

Increased bone formation

Osteoblasts have lost inhibition and are creating bone like no tomorrow

Question 20

Osteocytes

Answer 20

Imbedded in matrix lacunae
Long dendritic processes in canaliculi
Mechanosenor cells
Regulate: osteoblast differentiation via SOST
Bone Remodeling and phosphate metabolism

Question 21

Osteoclasts

Answer 21

Form Howship’s Lacunae where they deposit acid
Attached to bone matrix via talin and vinculin (focal adhesions)
Produce carbonic anhydrase
Pump H+ into Howships lacunae via ATPase
Lifespan 2 weeks

Question 22

Osteoclast Differentiation

Answer 22

Immature Osteoblasts produce M-CSF
M-CSF stimulates CFU-GM cell
Pre-Osteoclast forms from CFU-GM
Pre-Osteocalst Receptor RANK binds to RANKL and differentiates into osteoclast

Question 23

Types of Bone Formation

Answer 23

Intramembraneous
Bone forms directly from mesenchyme
i.e. skull, mandible, clavicle

Endochondral
Bone replaces a cartilage template
Base of the skull, vertebrae, limbs

Question 24

PTHrp

Answer 24

Parathyroid Hormone Related Protein
Most concentrated at the diaphysis
Signals chondrocytes to proliferate
Prevents chondrocyte hypertrophy

Question 25

3 Key aspects of Bone Remodeling

Answer 25

Mineral Homeostasis
Repair Microdamage
Adapt to mechanical forces

Question 26

Bone Remodeling Process

Answer 26

Takes 6-9 months

Activation > Resorption > Reversal > Formation

Question 27

BMU

Answer 27

Basic Multicellular Unit
Contains osteoclasts and osteoblasts
BMUs tunnel longitudinally through corical bone forming new Haversian systems

Question 28

Mechanical Loading vs Unloading

Answer 28

Mechanical loading prevents osteocyte apoptosis
Mechanical Unloading promotes apoptosis
Mechanical Loading prevents SOST signaling and promotes Wnt signaling