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Biochem Exam 5 > 11/13: Chondrocytes and Cartilage > Flashcards

11/13: Chondrocytes and Cartilage Flashcards

1
Q

What is cartilage?

A

Specialized connective tissue
Avascular

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2
Q

What does cartilage contain?

A

Limited regenerative capacity
Gelatinous ground substance

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3
Q

Where is cartilage found?

A

Locations where support, flexibility, resistance to compression

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4
Q

What is cartilage important in?

A

Embryonic bone formation

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5
Q

What is important for longitudinal bone growth?

A

Growth plate cartilage

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6
Q

What makes up hyaline cartilage?

A

Protein fibers = predominantly collagen (II,X)

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7
Q

Where is hyaline cartilage found?

A

− Growth plate
− Precursor to bone in embryonic skeleton
− Joint articular surfaces (reduces
friction/acts as shock absorber)
− Costal (rib) cartilages
− Cartilage in nose, ears, trachea, larynx,
smaller respiratory tubes

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8
Q

What is elastic cartilage?

A

Type II collagen with lots of elastic fibers (elastin), making it more flexible

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9
Q

Where is elastic cartilage found in?

A

− pharyngotympanic (eustachian) tubes
− epiglottis
− ear lobes

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10
Q

What is fibrocartilage made of?

A

Mixture of fibrous tissue (type I collagen containing) and hyaline cartilage

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11
Q

Where is fibrocartilage found in?

A

− Pubic symphysis
− Intervertebral disks
− Temporomandibular joint (TMJ)

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12
Q

What does the ECM of fibrocartilage contain?

A

Type I and Type II collagen

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13
Q

What are the steps of endoochondral bone formation?

A
  1. Mesenchymal condensation
  2. differentiation
  3. blood vessels initiate cartilage destruction/bone
    formation in center of developing element
  4. Secondary ossification centers formed following vascular invasion
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14
Q

Proliferation of columnar chondrocytes and expansion of chondrocyte size in hypertrophic region is the principle engine for?

A

Longitudinal bone growth

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15
Q

What is the master regulator of chondrocyte differentiation?

A

SOX9

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16
Q

What replaces SOX9 in cartilage differentiation?

A

RUNX2
OSX

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17
Q

What drives differentiation down chondrocyte pathway?

A

SOX9

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18
Q

What is expressed in chondroprogenitors/proliferating chondrocytes?

A

activation of SOX9

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19
Q

Why must SOX9 be downregulated?

A

To allow chondrocytes to mature

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20
Q

What does SOX9 inhibit?

A

RUNX2

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21
Q

What is expressed in prehypertrophic and hypertrophic chondrocytes?

A

RUNX2/OSX

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22
Q

What are important regulators of hypertrophy?

A

RUNX2/OSX

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23
Q

What does RUNX2 homozygous deletion cause?

A

Delayed chondrocyte maturation - failure to form bone

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24
Q

What are key regulators of chondrogenesis and are the two ligands chondrocytes bind to?

A

LHH and PTHrP

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25
Q

What are LHH and PTHrP receptors?

A

PTC1 and PTH1R

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26
Q

What regualtes chondrocyte proliferation/differentiation and determine length of the proliferating columns of chondrocytes?

A

Ihh and PTHrP

27
Q

What determines when chondrocytes enter hypertrophy?

A

Ihh and PTHrP

28
Q

What is the principle engine for bone growth?

A

Chondrocyte hypertrophy

29
Q

What is Ihh/PTHrP axis very important in?

A

Regulating bone longitudinal bone growth

30
Q

What is PTHrP produced by?

A

Early proliferative chondrocytes near ends of bone/growth plate

31
Q

What does PTHrP act on/

A

PTH1R receptor in late proliferating/prehypertrophic dhoncroycytes to keep them proliferating

32
Q

What happens when chondrocytes are far enough from source?

A

No longer stimulated by PTHrP -> stop proliferating -> become hypertrophic -> synthesize Ihh

33
Q

What stimulates chondrocyte proliferation>

A

Ihh

34
Q

What does Ihh act on to stimulate?

A

Early proliferating cells; producting more PTHrP

35
Q

What cells does Ihh induce and what does this form?

A

Perioteal cells; mineralized bone collar

36
Q

What does the feedback loop ensure?

A

Once cells enter hypertrophy (a one way trip eventually resulting in apoptosis!) they
produce Ihh then PTHrP to ensure proliferation of a
continual supply of chondrocytes to replace them

37
Q

What is a critical regulator of chondrocyte proliferation/differentiation?

A

FGF signaling

38
Q

When is FGFR3 expressed?

A

In proliferating/prehypertrophic chondrocytes

39
Q

What is FGFR3 signaling important in?

A

Regulatory step that limits chondrocyte proligeration

40
Q

What does FGFR3 suppress?

A

Ihh

41
Q

What is the major fibrillar collagen in cartilage?

A

Type II collagen

42
Q

What is the major collagen expressed in hypertrophic cartilage?

A

Type X collagen

43
Q

What are the 1st and 2nd suar residues in glycosaminoglycans?

A

1st = amino sugar
2nd = uronic acid

44
Q

What are 4 main groups of GAGS?

A

Hyaluronan
Chondroitin sulfate and dermatan sulfate
Heparan sulfate and heparin
Keratan sulfate

45
Q

What are the major proteoglycans of skeletal tissues?

A

Aggrecan
Versican

46
Q

What are small leucine rich proteoglycans?

A

Decorin
Biglycan
Fibromodulin
Osteoglycin

47
Q

What does the aggrecan core protein have?

A

Keratan sulphate
Chondroitin sulfate GAG chains

48
Q

What may regulate calcification?

A

Aggrecan

49
Q

What happens when there are
mutations in genes involved
with cartilage differentiation
and function?

A

Chondrodysplasias

50
Q

What is a hereditary skeletal disorders characterized by abnormal growth plate function leading to skeletal
deformities/growth defects?

A

Chondrodysplasias

51
Q

What is camplomelic dysplasia caused by?

A

Heterozygous loss of function mutation in SOX9

52
Q

What does camplomelic dysplasia affect?

A

Development of skeleton/reproductive system

53
Q

What does impaired PTHrP signaling lead to?

A

late proliferating/prehypertrophic chondrocytes
will enter hypertrophy too soon (premature growth plate
maturation/skeletal maturation)

54
Q

What does impaired Ihh signaling lead to?

A

no replacement of proliferating cells once
they have gone into hypertrophy
(premature closing of the growth plate)

55
Q

What happens when both PTHrP and IHH signaling goes wrong?

A

Growth retardation (dwarfism)

56
Q

What is required for normal chondrocyte differentiation/bone development in humans?

A

Ihh/PTHrP signaling

57
Q

What is the most common form of short limbed dwarfism?

A

Achondroplasia

58
Q

What is achondroplasia caused by?

A

Mutation in FGF receptor 3 (FGFR3)

59
Q

What are the types of clinical severity of type II collagen mutations?

A

Lethal
Severe
Mild

60
Q

What are mutations in type II collagen linked to?

A

Chondrodysplasias

61
Q

What is spondyloepiphyseal dysplasia (SED) a mutation in?

A

COL2A1 gene (type 2 collagen)

62
Q

What is Schmid-type meetaphyseal chondrodysplasia a mutatoin in?

A

COL10A1 (type X collagen)

63
Q

What are the 3 types of chondrodysplasias?

A
  1. Mutations in transcription factors
    - SOX9
  2. Mutations in cartilage extracellular amtrix components
    - Type II collagen
    - Type X collagen
    - aggrecan
  3. Mutations in signaling molecules and their receptors
    - PTHrP,IHH, PTH1R loss/gain of function
    - FGFR3

Biochem Exam 5 (11 decks)

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