11/8: Biochemistry of Bone Formation COPY

Question 1

1. What are the four phases of skeletal development?

Answer 1

(MIMD)
1. Migration
2. Interaction
3. Mesenchymal condensation
4. Differentiation

Question 2

2. What are the two types of bone formation?

Answer 2

a. 1. Endochondral
b. 2. Intramembranous

Question 3

3. Which bone formation type is indirect?

Answer 3

Endochondral

Question 4

What occurs in endochondral bone formation?

Answer 4

The bone starts as cartilage

Question 5

What bones are usually endochondral?

Answer 5

Bones that bear weight

Question 6

What bone formation is direct?

Answer 6

Intramembranous

Question 7

7. Why is it intramembranous bone formation direct?

Answer 7

Because the mesenchymal cells become osteoblasts with no cartilage intermediate

Question 8

8. Where is intramembranous bone formation restricted at?

Answer 8

a. It is restricted to the cranial vault and facial bones

Question 9

9. What molecules attract hypertrophic chondrocytes to blood vessels to invade?

Answer 9

VEGF

Question 10

10. When does growth plate fusion occur?

Answer 10

Age 14-20

Question 11

11. When do secondary ossification centers appear?

Answer 11

a. Around the time of birth

Question 12

12. What is the first type of bone produced?

Answer 12

a. Woven bone/Primary bone

Question 13

13. When is woven bone most often found?

Answer 13

During fractures

Question 14

What is woven immature bone replaced with?

Answer 14

Lamellar bone

Question 15

What can lamellar bone be classified into?

Answer 15

1. Compact bone
2. Cancellous bone

Question 16

What are the three main bone cell types?

Answer 16

1. Osteoclasts
2. Osteoblasts
3. Osteocytes

Question 17

What is unique about osteoblasts, chondroblasts, myoblasts, and adipocytes?

Answer 17

They all originate from a mesenchymal progenitor

Question 18

What type of collagen is produced from osteoblasts?

Answer 18

Type 1

Question 19

What are the two transcription factors used in osteoblasts?

Answer 19

RUNX2
Osterix

Question 20

What are the extracellular matrix proteins used in osteoblasts?

Answer 20

(BOOT)
Type 1 collagen
Osteopontin
Osteocalcin
Bone sialoprotein

Question 21

What does RUNX2 and Osterix do?

Answer 21

RUNX2
i. Allows mesenchyme to mature into immature osteoblasts Osterix
i. Allows immature osteoblasts to mature into mature osteoblasts

Question 22

What molecules inhibit these steps?

Answer 22

B-catenin

Question 23

What is the master transcription factor for osteoblasts?

Answer 23

RUNX2

Question 24

24. In humans, if RUNX2 is mutated what occurs?

Answer 24

a. Cleidocranial dysplasia

Question 25

Is cleidocranial dysplasia an autosomal dominant or haploinsufficient mutation of RUNX2?

Answer 25

Both

Question 26

What molecules does osterix control?

Answer 26

Type 1 collagen Osteocalcin Osteopontin

Question 27

What do mutations in osterix cause in humans?

Answer 27

Osteogenesis imperfecta type 12

Question 28

28. What two key molecules regulate osteoblast differentiation besides RUNX2 and Osterix?

Answer 28

1. BMPS 2. WNT/B-Catenin

Question 29

What do BMPs do?

Answer 29

Maintain adult bone homeostasis

Question 30

What is FOP (Fibrodysplasia Ossificans Progressiva)?

Answer 30

Heterotopic bone formation that results in a stone man appearance due to a BMP type 1 mutation

Question 31

What does this mean in regards to FOP?

Answer 31

Everytime soft tissue damage occurs, bone take its place

Question 32

What is the high bone mass phenotype caused by?

Answer 32

Mutations of LRP5

Question 33

What does the LRP5 mutations affect?

Answer 33

Wnt/B-Catenin signaling

Question 34

What does inactivating mutations of LRP5 cause?

Answer 34

a. Low bone mass

Question 35

35. What initiates the first phase of mineralization?

Answer 35

a. Matrix vesicle secretion

Question 36

36. What initiates the second phase of mineralization?

Answer 36

a. Propagation of mineralized collagen fibers

Question 37

37. What enzyme is highly expressed in osteoblasts and odontoblasts?

Answer 37

a. Alkaline phosphatase (AP)

Question 38

38. What does AP do?

Answer 38

a. Hydrolyzes pyrophosphate which leads to mineralization

Question 39

39. Why is hydrolyzing pyrophosphate important in the mineralization process?

Answer 39

a. Because pyrophosphate is an inhibitor of mineralization

Question 40

40. What disorder is associated with mutations in alkaline phosphate?

Answer 40

a. Hypophosphatasia

Question 41

41. What gene causes this?

Answer 41

a. TNSALP

Question 42

42. Is there a master transcriptional gene identified for osteocytes yet?

Answer 42

No

Question 43

43. What gene controls the transcription factors for osteocytes?

Answer 43

Mef2c

Question 44

44. What are the potential functions of osteocytes?

Answer 44

a. Mechanosensors b. Bone resorption and bone formation c. Regulation of mineralization d. Mineral homeostasis

Question 45

45. What gene is used by osteocytes to regulate osteoblasts?

Answer 45

Sclerostin

Question 46

46. What cells express sclerostin?

Answer 46

a. Osteocytes b. Cementocytes c. Odontoblasts

Question 47

47. How does sclerostin negative regulate bone formation?

Answer 47

a. Through the antagonistic affect of Wnt/Beta-catenin signaling

Question 48

48. What do sclerostin mutations cause?

Answer 48

a. Vanbuchems disease

Question 49

49. What is Van Buchems disease?

Answer 49

a. Bone mass increases in craniofacial skeleton (Crimson chin disease)

Question 50

50. What genes do osteocytes express that are important in phosphate homeostasis?

Answer 50

a. FGF23 b. DMP1 c. PHEX