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D1 Fall - Biochem > 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
What are the two ligands chondrocytes bind to?
PTHrP lHH
26
What are the receptors for PTHrP and IHH?
PTC1 and PTH1R
27
What do the ligands and their receptor binding regulate?
Chondrocyte proliferation/differentiation
28
Do the ligands and their receptors also determine when chondrocytes enter hypertrophy?
Yes
29
What are the 6 steps used by IH/PTHrP in regulating chondrocyte differentiation?
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
What does this loop ensure?
It ensures that there is always a constant supply of chondrocytes replacing dead chondrocytes
31
31. Which fibroblast growth factors is important in chondrocyte growth?
FGF
32
32. What is FGFR3 used as?
A regulatory step in the PTHrP and IHH cycle to ensure chondrocytes do not over proliferate
33
33. Does FGFR3 inhibit IHH?
Yes
34
34. What are the 3 key ECM proteins expressed in cartilage?
a. Type II collagen b. Aggrecan c. Type X collagen
35
35. Is type II collagen a heterotrimer or homotrimer?
Homo
36
36. What gene codes for type II collagen?
COL2A1
37
37. What cartilage type expressed type X collagen?
Hypertrophic cartilage
38
38. Is type X collagen a homotrimer or heterotrimer?
Homo
39
What genes code for type X collagen?
COL10A1
40
What is the first sugar residue in a GAG?
Amino sugar i. Either usually N-acetylglucosamine or N-acetylgalactosamine
41
What is the second sugar residue in a GAG?
Uronic acid
42
What are the 4 main GAG types in cartilage?
1. Hyaloruan 2. Chondroitin sulfate/Dermatan sulfate 3. Heparan sulfate/Heparin 4. Keratan sulfate
43
What are most GAGs found covalently attached to?
Proteoglycans
44
What are the two major proteoglycans?
Aggrecan Versican
45
What GAG types are found attached to aggrecan?
a. Keratan sulfate b. Chondroitin sulfate
46
46. What does aggrecan assemble with to form huge chains?
a. Hyaluronan
47
47. What disease results from mutations that affect cartilage differentiation and function?
a. Chondrodysplasisa
48
48. What does Chondrodysplasia cause?
a. Skeletal growth defects and deformities
49
49. What is camplomelic dysplasia?
a. A disease caused by a loss of function mutation in SOX9
50
50. Is Camplomelic Dysplasia life-threatening neonatally?
Yes
51
51. What can happen if PTHrP signaling is affected?
a. Prehypertrophic chondrocytes will enter hypertrophy too early and cause premature growth plate maturation
52
52. What can happen if IHH signaling is impaired?
a. Proliferating cells will not be replaced once they become hypertrophic
53
53. What do both scenarios lead to?
a. Growth retardation
54
54. What can GOF mutations in FGFR3 cause?
a. Achondroplasia
55
55. What does achondroplasia cause?
a. Short stature b. Short bones
56
56. What are the 3 types of mutations linked to collagen type II and chondrodysplasia
a. Lethal b. Severe c. Mild
57
57. What are the mild type II collagen chondroplasyia diseases?
a. Stickler syndrome
58
58. What are the severe type II collagen chondroplasyia diseases?
a. Spondyloepiphyseal dysplasia
59
59. What are the lethal type II collagen chondroplasyia diseases?
a. Achondrogenesis type II
60
60. What do all mutations that lead to achondrogenesis type II have in common?
a. They are all caused by the replacement of glycine to a bulkier amino acid in the triple helical region
61
61. What diseases are caused by COL10A1 gene mutations?
a. Schmid-Type Metaphyseal chondrodysplasia
62
62. Is spondyloepimetaphyseal dysplasia an autosomal recessive disease?
Yes
63
63. What causes spondyloepimetaphyseal dysplasia?
a. A mutation in aggrecan

D1 Fall - Biochem (29 decks)

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