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Biochem Final > 11/9: Osteoclasts, Osteoporosis and Fracture Healing > Flashcards

11/9: Osteoclasts, Osteoporosis and Fracture Healing Flashcards

1
Q

What lineage are osteoclasts derived from?

A

Hematopoietic lineage

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2
Q

Are mature osteoclasts multinucleated?

A

Yes

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3
Q

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

A

Ruffled border

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4
Q

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

A

Yes

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5
Q

Where does bone growth occur?

A

Epiphyseal plate

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6
Q

Why must modeling occur?

A

Because it is needed to maintain bone shape

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7
Q

What is the master transcription factor for osteoclasts?

A

NFATc1

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8
Q

What proteins regulate osteoclast activity

A

RANKL
M-CSF

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9
Q

What does RANKL do?

A

promotes fusion of osteoclasts and their differentiation

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10
Q

What does M-CSF do?

A

Promote osteoclast proliferation and survival

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11
Q

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

A

Through the generation of protons in the space

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12
Q

What proteins actively degrade the sealing zone?

A

a. Carbonic anhydrase II
b. ATPase pumps

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13
Q

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

A

~4.5

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14
Q

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

A

Chloride channel

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15
Q

What protein released by osteoclasts degrades matrix vesicles?

A

Cathepsin K

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16
Q

What does impaired osteoclast function lead to?

A

Osteoporosis

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17
Q

What are the two major clinical forms of impaired osteoclasts?

A

Autosomal dominant Autosomal recessive

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18
Q

What form is found in adults and is benign?

A

Autosomal dominant

19
Q

What form is found in infants and is malignant?

A

Autosomal recessive

20
Q

What proteins are commonly mutated that cause osteoporosis?

A

ATPase
Chloride channel
Cathepsin K

21
Q

What proteins are commonly mutated that cause osteoporosis?

A

ATPase
Chloride channel
Cathepsin K

22
Q

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

A

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

23
Q

What drug is of great use in combating osteoporosis?

A

Bisphosphonates

24
Q

What are bisphosphonate?

A

They are non-hydrolyzable analogs of pyrophosphates

25
Q

What do bisphosphonates inhibit?

A

Mineralization

26
Q

What can bisphosphonates cause?

A

Osteonecrosis of the jaw

27
Q

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

A
  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
28
Q

What is the timeline of fracture healing

A
  1. Inflammatory/reactive phase: days to weeks
  2. Reparative phase: weeks to months
  3. Remodeling phase: months to years
29
Q

Is the pathogenesis of BONJ understood?

A

no

30
Q

What are the 4 stages of fracture healing?

A

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

31
Q

What cytokines are released when a hematoma is formed?

A

Tumor necrosis factor
Interleukins

32
Q

What does both TNF and IL release lead to?

A

Inflammatory cell recruitment and infiltration

33
Q

What tissue gets deposited when the fibrocartilage callus is formed?

A

Granulation tissue

34
Q

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

A

They start endochondral bone formation

35
Q

Where is the major source of osteogenic precursors found at?

A

Periosteum

36
Q

What are the three cells that can become osteogenic?

A
  1. Mesenchymal stem cells
  2. Pericyte
  3. Muscle satellite cells
37
Q

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

A

It undergoes endochondral ossification

38
Q

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

A

Woven bone

39
Q

Are genes expressed during fracture healing?

A

yes

40
Q

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

A
  1. Pro-inflammatory cytokines
  2. TGF beta
  3. Angiogenic factors
41
Q

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

A
  1. Recruitment of other inflammatory cells and mesenchymal stem cells differentiation
  2. Apoptosis of hypertrophic chondrocytes
  3. Osteoclast formation
42
Q

What does TGF, BMP, and GDF proteins do?

A
  1. Promote ECM synthesis and assembly
  2. Promote osteogenic differentiation
  3. Cell proliferation
43
Q

What angiogenic factors are released during fracture repair?

A

VEGF
PDGF
Angiopoietin

44
Q

What do these factors do?

A

Cause the promotion of vascular ingrowth

Biochem Final (7 decks)

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