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Biochem Final > 11/8: Biochemistry of Bone Formation > Flashcards

11/8: Biochemistry of Bone Formation Flashcards

1
Q
  1. What are the four phases of skeletal development?
A

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

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2
Q
  1. What are the two types of bone formation?
A

a. 1. Endochondral
b. 2. Intramembranous

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3
Q
  1. Which bone formation type is indirect?
A

Endochondral

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4
Q

What occurs in endochondral bone formation?

A

The bone starts as cartilage

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5
Q

What bones are usually endochondral?

A

Bones that bear weight

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6
Q

What bone formation is direct?

A

Intramembranous

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7
Q
  1. Why is it intramembranous bone formation direct?
A

Because the mesenchymal cells become osteoblasts with no cartilage intermediate

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8
Q
  1. Where is intramembranous bone formation restricted at?
A

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

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

VEGF

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10
Q
  1. When does growth plate fusion occur?
A

Age 14-20

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11
Q
  1. When do secondary ossification centers appear?
A

a. Around the time of birth

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12
Q
  1. What is the first type of bone produced?
A

a. Woven bone/Primary bone

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13
Q
  1. When is woven bone most often found?
A

During fractures

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14
Q

What is woven immature bone replaced with?

A

Lamellar bone

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15
Q

What can lamellar bone be classified into?

A
  1. Compact bone
  2. Cancellous bone
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16
Q

What are the three main bone cell types?

A
  1. Osteoclasts
  2. Osteoblasts
  3. Osteocytes
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17
Q

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

A

They all originate from a mesenchymal progenitor

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18
Q

What type of collagen is produced from osteoblasts?

A

Type 1

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19
Q

What are the two transcription factors used in osteoblasts?

A

RUNX2
Osterix

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20
Q

What are the extracellular matrix proteins used in osteoblasts?

A

(BOOT)
Type 1 collagen
Osteopontin
Osteocalcin
Bone sialoprotein

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21
Q

What does RUNX2 and Osterix do?

A

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

22
Q

What molecules inhibit these steps?

A

B-catenin

23
Q

What is the master transcription factor for osteoblasts?

A

RUNX2

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

a. Cleidocranial dysplasia

25
Q

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

A

Both

26
Q

What molecules does osterix control?

A

Type 1 collagen
Osteocalcin
Osteopontin

27
Q

What do mutations in osterix cause in humans?

A

Osteogenesis imperfecta type 12

28
Q
  1. What two key molecules regulate osteoblast differentiation besides RUNX2 and Osterix?
A
  1. BMPS
  2. WNT/B-Catenin
29
Q

What do BMPs do?

A

Maintain adult bone homeostasis

30
Q

What is FOP (Fibrodysplasia Ossificans Progressiva)?

A

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

31
Q

What does this mean in regards to FOP?

A

Everytime soft tissue damage occurs, bone take its place

32
Q

What is the high bone mass phenotype caused by?

A

Mutations of LRP5

33
Q

What does the LRP5 mutations affect?

A

Wnt/B-Catenin signaling

34
Q

What does inactivating mutations of LRP5 cause?

A

a. Low bone mass

35
Q
  1. What initiates the first phase of mineralization?
A

a. Matrix vesicle secretion

36
Q
  1. What initiates the second phase of mineralization?
A

a. Propagation of mineralized collagen fibers

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

a. Alkaline phosphatase (AP)

38
Q
  1. What does AP do?
A

a. Hydrolyzes pyrophosphate which leads to mineralization

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

a. Because pyrophosphate is an inhibitor of mineralization

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

a. Hypophosphatasia

41
Q
  1. What gene causes this?
A

a. TNSALP

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

No

43
Q
  1. What gene controls the transcription factors for osteocytes?
A

Mef2c

44
Q
  1. What are the potential functions of osteocytes?
A

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

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

Sclerostin

46
Q
  1. What cells express sclerostin?
A

a. Osteocytes
b. Cementocytes
c. Odontoblasts

47
Q
  1. How does sclerostin negative regulate bone formation?
A

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

48
Q
  1. What do sclerostin mutations cause?
A

a. Vanbuchems disease

49
Q
  1. What is Van Buchems disease?
A

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

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

a. FGF23
b. DMP1
c. PHEX

Biochem Final (7 decks)

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