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Biochem Final > 11/13: Chondrocytes & Cartilage > Flashcards

11/13: Chondrocytes & Cartilage Flashcards

1
Q
  1. What is cartilage?
A

a. Specialized connective tissue

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2
Q
  1. What makes cartilage regeneration limited?
A

a. Its avascular nature

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3
Q
  1. What are the three types of cartilage?
A
  1. Hyaline cartilage
  2. Elastic cartilage
  3. Fibrocartilage
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4
Q
  1. What collagen types make up hyaline cartilage?
A

a. 2 and 10

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5
Q
  1. Is hyaline cartilage the most abundant type of cartilage found in the body?
A

a. Yes

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6
Q
  1. Where is hyaline cartilage found?
A

a. Growth plates
b. Skeleton precursor
c. Joint articular surfaces
d. Costal cartilages
e. Nose, ears, trachea, larynx

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7
Q

What collagen type is found in elastic cartilage?

A

a. Type 2 collagen

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8
Q
  1. Where is elastic cartilage found?
A

a. Pharyngotympanic tubes
b. Epiglottis
c. Ear lobes

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9
Q
  1. What collagen type makes up fibrocartilage?
A

a. Type 1 collagen and hyaline cartilage type 2

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10
Q
  1. Where is fibrocartilage found at?
A

(PIT)
a. Pubic symphysis
b. IV discs
c. TMJ

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11
Q
  1. What do all osteoblasts, chondrocytes, myoblasts, and adipocytes start as before they differentiate?
A

a. Mesenchymal progenitor

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12
Q

What are the different zones of bone growth?

A

Mnemonic: Real, People, May, Have, Career, Options
a. Zone of reserve cartilage
b. Zone of proliferation
c. Zone of maturation
d. Zone of hypertrophy
e. Zone of degeneration/calcification
f. Zone of ossification

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13
Q

What is the principal engine for longitudinal bone growth?

A

a. Proliferation of columnar chondrocytes and expansion of chondrocyte size

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14
Q

What is the main master transcription factor in chondrocyte differentiation?

A

SOX9

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15
Q

What does SOX9 do to mesenchymal cells?

A

a. Turns them into chondrocytes and flat columnar chondrocytes

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16
Q

What turns flat columnar chondrocytes into terminal hypertrophic chondrocytes?

A

a. RUNX2
b. OSX

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17
Q
  1. Does SOX9 drive differentiation down the chondrocyte pathway?
A

Yes

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18
Q
  1. What cells express SOX9?
A

a. Chondroprogenitors and proliferating chondrocytes

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19
Q

In order for prehypertrophic and hypertrophic chondrocytes to proliferate, what must be down regulated?

A

SOX9

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20
Q

Does SOX9 inhibit RUNX2?

A

Yes

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21
Q

If Runx2 is deleted, what happens to chondrocyte?

A

They fail to mature

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22
Q

What collagen type do hypertrophic chondrocytes express?

A

Type 10

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23
Q

What do the chondrocytes express in order to allow for mineralization?

A

Alkaline phosphatases

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24
Q

What do the chondrocytes express in order to allow for vascular invasion to occur?

A

MMP13 and VEGF

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25
Q

What are the two ligands chondrocytes bind to?

A

PTHrP
lHH

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26
Q

What are the receptors for PTHrP and IHH?

A

PTC1 and PTH1R

27
Q

What do the ligands and their receptor binding regulate?

A

Chondrocyte proliferation/differentiation

28
Q

Do the ligands and their receptors also determine when chondrocytes enter
hypertrophy?

A

Yes

29
Q

What are the 6 steps used by IH/PTHrP in regulating chondrocyte differentiation?

A
  1. PTHrP produced early by chondrocytes near growth plate
  2. PTHrP activates when it binds to PTH1R later in growth stopping chondrocytes from proliferation
  3. Chondrocytes stopped become prehypertrophic and produce IHH
  4. IHH causes chondrocytes to proliferate
  5. IHH acts upon adjacent cells causing them to produce more PTHrP
  6. Mineralized bone collar forms
30
Q

What does this loop ensure?

A

It ensures that there is always a constant supply of chondrocytes replacing dead chondrocytes

31
Q
  1. Which fibroblast growth factors is important in chondrocyte growth?
A

FGF

32
Q
  1. What is FGFR3 used as?
A

A regulatory step in the PTHrP and IHH cycle to ensure chondrocytes do not over proliferate

33
Q
  1. Does FGFR3 inhibit IHH?
A

Yes

34
Q
  1. What are the 3 key ECM proteins expressed in cartilage?
A

a. Type II collagen
b. Aggrecan
c. Type X collagen

35
Q
  1. Is type II collagen a heterotrimer or homotrimer?
A

Homo

36
Q
  1. What gene codes for type II collagen?
A

COL2A1

37
Q
  1. What cartilage type expressed type X collagen?
A

Hypertrophic cartilage

38
Q
  1. Is type X collagen a homotrimer or heterotrimer?
A

Homo

39
Q

What genes code for type X collagen?

A

COL10A1

40
Q

What is the first sugar residue in a GAG?

A

Amino sugar
i. Either usually N-acetylglucosamine or N-acetylgalactosamine

41
Q

What is the second sugar residue in a GAG?

A

Uronic acid

42
Q

What are the 4 main GAG types in cartilage?

A
  1. Hyaloruan
  2. Chondroitin sulfate/Dermatan sulfate
  3. Heparan sulfate/Heparin
  4. Keratan sulfate
43
Q

What are most GAGs found covalently attached to?

A

Proteoglycans

44
Q

What are the two major proteoglycans?

A

Aggrecan
Versican

45
Q

What GAG types are found attached to aggrecan?

A

a. Keratan sulfate
b. Chondroitin sulfate

46
Q
  1. What does aggrecan assemble with to form huge chains?
A

a. Hyaluronan

47
Q
  1. What disease results from mutations that affect cartilage differentiation and function?
A

a. Chondrodysplasisa

48
Q
  1. What does Chondrodysplasia cause?
A

a. Skeletal growth defects and deformities

49
Q
  1. What is camplomelic dysplasia?
A

a. A disease caused by a loss of function mutation in SOX9

50
Q
  1. Is Camplomelic Dysplasia life-threatening neonatally?
A

Yes

51
Q
  1. What can happen if PTHrP signaling is affected?
A

a. Prehypertrophic chondrocytes will enter hypertrophy too early and cause premature growth plate maturation

52
Q
  1. What can happen if IHH signaling is impaired?
A

a. Proliferating cells will not be replaced once they become hypertrophic

53
Q
  1. What do both scenarios lead to?
A

a. Growth retardation

54
Q
  1. What can GOF mutations in FGFR3 cause?
A

a. Achondroplasia

55
Q
  1. What does achondroplasia cause?
A

a. Short stature
b. Short bones

56
Q
  1. What are the 3 types of mutations linked to collagen type II and chondrodysplasia
A

a. Lethal
b. Severe
c. Mild

57
Q
  1. What are the mild type II collagen chondroplasyia diseases?
A

a. Stickler syndrome

58
Q
  1. What are the severe type II collagen chondroplasyia diseases?
A

a. Spondyloepiphyseal dysplasia

59
Q
  1. What are the lethal type II collagen chondroplasyia diseases?
A

a. Achondrogenesis type II

60
Q
  1. What do all mutations that lead to achondrogenesis type II have in common?
A

a. They are all caused by the replacement of glycine to a bulkier amino acid in the triple helical region

61
Q
  1. What diseases are caused by COL10A1 gene mutations?
A

a. Schmid-Type Metaphyseal chondrodysplasia

62
Q
  1. Is spondyloepimetaphyseal dysplasia an autosomal recessive disease?
A

Yes

63
Q
  1. What causes spondyloepimetaphyseal dysplasia?
A

a. A mutation in aggrecan

Biochem Final (7 decks)

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