BC: Lecture 2

Question 1

What lineage are osteoclasts derived from?

Answer 1

Hematopoietic lineage

Question 2

Are mature osteoclasts multinucleated?

Answer 2

Yes

Question 3

What does expression of proton pumps to reduce pH around bone cause the formation of?

Answer 3

Ruffled border

Question 4

Are osteoclasts responsible for anything that has to do with bone resorption, including
tooth roots and alveolar bone?

Answer 4

Yes

Question 5

Where does bone growth occur?

Answer 5

Epiphyseal plate

Question 6

Why must modeling occur?

Answer 6

Because it is needed to maintain bone shape

Question 7

What is the master transcription factor for osteoclasts?

Answer 7

NFATc1

Question 8

What proteins regulate osteoclast activity

Answer 8

RANKL
M-CSF

Question 9

What does RANKL do?

Answer 9

promotes fusion of osteoclasts and their differentiation

Question 10

What does M-CSF do?

Answer 10

Promote osteoclast proliferation and survival

Question 11

Once the sealing zone has formed, how is the bone actively degraded?

Answer 11

Through the generation of protons in the space

Question 12

What proteins do this?

Answer 12

a. Carbonic anhydrase II
b. ATPase pumps

Question 13

What is the pH of the resorption bay generated by the osteoclasts?

Answer 13

~4.5

Question 14

What channel maintains the charge in the space created by the sealing zone?

Answer 14

Chloride channel

Question 15

What protein released by osteoclasts degrades matrix vesicles?

Answer 15

Cathepsin K

Question 16

What does impaired osteoclast function lead to?

Answer 16

Osteoporosis

Question 17

What are the two major clinical forms of impaired osteoclasts?

Answer 17

Autosomal dominant Autosomal recessive

Question 18

What form is found in adults and is benign?

Answer 18

Autosomal dominant

Question 19

What form is found in infants and is malignant?

Answer 19

Autosomal recessive

Question 21

What proteins are commonly mutated that cause osteoporosis?

Answer 21

ATPase
Chloride channel Cathepsin K

Question 22

What do you have to be defined as to be clinically diagnosed with osteoporosis?

Answer 22

You have to be defined as having a BMD >2.5 SD below the average

Question 23

What drug is of great use in combating osteoporosis?

Answer 23

Bisphosphonates

Question 24

What are bisphosphonate?

Answer 24

They are non-hydrolyzable analogs of pyrophosphates

Question 25

What do bisphosphonates inhibit?

Answer 25

Mineralization

Question 26

What can bisphosphonates cause?

Answer 26

Osteonecrosis of the jaw

Question 27

What are the criteria needed to be classified with osteonecrosis of the jaw?

Answer 27

1. Current or previous treatment with a bisphosphonate 2. Exposed, necrotic bone in the maxillofacial region that has been present for 8 weeks 3. No history of radiation therapy to the jaw

Question 28

What is the timeline of fracture healing

Answer 28

1. Inflammatory/reactive phase: days to weeks 2. Reparative phase: weeks to months 3. Remodeling phase: months to years

Question 29

Is the pathogenesis of BONJ understood?

Answer 29

no

Question 30

What are the 4 stages of fracture healing? (VFTB)

Answer 30

1. Vascular hematoma formation 2. Fibrocartilage callus formation 3. Tissue metaplasia 4. Bone remodeling/turnover

Question 31

What cytokines are released when a hematoma is formed?

Answer 31

Tumor necrosis factor Interleukins

Question 32

What does both TNF and IL release lead to?

Answer 32

Inflammatory cell recruitment and infiltration

Question 33

What tissue gets deposited when the fibrocartilage callus is formed?

Answer 33

Granulation tissue

Question 34

Some ends of the bone break will become hypoxic, when this occurs, what happens to the mesenchymal stem cells?

Answer 34

They start endochondral bone formation

Question 35

Where is the major source of osteogenic precursors found at?

Answer 35

Periosteum

Question 36

What are the three cells that can become osteogenic?

Answer 36

a. 1. Mesenchymal stem cells b. 2. Pericyte c. 3. Muscle satellite cells

Question 37

In formation of the bony callus, what happens to the cartilage?

Answer 37

It undergoes endochondral ossification

Question 38

Once the endochondral ossification is completed in the bony callus, what bone type is formed?

Answer 38

Woven bone

Question 39

Are genes expressed during fracture healing?

Answer 39

yes

Question 40

What are the 3 main signaling molecules that are important in fracture healing?

Answer 40

a. 1. Pro-inflammatory cytokines b. 2. TGF beta c. 3. Angiogenic factors

Question 41

When TNF and Interleukins get released, what does their release cause?

Answer 41

1. Recruitment of other inflammatory cells and mesenchymal stem cells differentiation 2. Apoptosis of hypertrophic chondrocytes 3. Osteoclast formation

Question 42

What does TGF, BMP, and GDF proteins do?

Answer 42

1. Promote ECM synthesis and assembly 2. Promote osteogenic differentiation 3. Cell proliferation

Question 43

What angiogenic factors are released during fracture repair?

Answer 43

VEGF PDGF Angiopoietin

Question 44

What do these factors do?

Answer 44

Cause the promotion of vascular ingrowth