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Biochem > Lecture 45- Chondrocytes and Cartilage > Flashcards

Lecture 45- Chondrocytes and Cartilage Flashcards

1
Q

what is cartilage

A

specialized avascular connective tissue with limited regenerative capacity

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2
Q

what does cartilage contain

A

gelatinous ground substance with collagen and elastic protein fibers

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3
Q

where is cartilage found

A

in locations where support, flexibility, resistance to compression are important

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4
Q

what type of embyronic bone formation is cartilage important in

A

endochondral

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5
Q

what is growth plate cartilage important for

A

longitudinal bone growth

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6
Q

describe hyaline cartilage

A
  • predominantly type 2 collagen and 10
  • glossy appearance with evenly dispersed chondrocytes
    -most abundant type in body
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7
Q

where is hyaline cartilage found

A

-growth plate
-precursor to bone in embryonic skeleton
-joint articular surfaces
- costal cartilages
-cartilage in nose, ears, trachea, larynx, smaller respiratory tubes

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8
Q

describe elastic cartilage

A

-type 2 collagen with a lot of elastic fibers

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9
Q

where is elastic cartilage found

A

eustachian tubes, epiglottis, and ear lobes

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10
Q

describe fibrocartilage

A

mixture of type 1 collagen and hyaline cartilage with chondrocytes dispersed among fine collagen fibers in layered arrays

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11
Q

where is fibrocartilage found

A

pubic symphysis, intervertebral disks, TMJ

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12
Q

what is the principle engine for longitudinal bone growth

A

proliferation of columnar chondrocytes and expansion of chondrocyte size in hypertrophic region

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13
Q

what transcription factors are important in chondrocyte differentiation

A

mainly SOX9, also RUNX2, and OSX

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14
Q

what are the major signaling molecules in chondrocyte differentiation

A

IHH, PTHrP, FGFs and VEGF

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15
Q

what are the major receptors for signaling molecules in chondrocyte differentiation

A

PTC1, PTH1R, FGFR3

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16
Q

what are the major extracellular matrix components

A

COL2A1, ACAn, and COL10A1

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17
Q

what are the major enzymes/proteases involved in chondrocyte differentiation

A

TNSALP, and MMP13

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18
Q

what does SOX9 do

A

drives differentiation down chondrocyte pathway

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19
Q

where is SOX9 expressed

A

in chondroprogenitors/proliferating chondrocytes

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20
Q

what must happen to SOX9 for chondrocytes to mature

A

it must be downregulated

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21
Q

what does SOX9 inhibit

A

RUNX2

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22
Q

what is RUNX2/OSX expressed in

A

prehypertrophic and hypertrophic chondrocytes

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23
Q

what is RUNX2/OSX an important regulator of

A

hypertrophy

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24
Q

what happens in hypertrophy of chondrocytes

A

-chondrocytes swell in size
- express type 10 collagen
- express alkaline phosphatase
- express MMP13/VEGF
-eventually undergo apoptosis

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25
what do Ihh and PTHrP regulate
chondrogenesis and longitudinal bone growth
26
what do coordinated actions of Ihh and PTHrP signaling through their receptors regulate
chondrocyte proliferation/differentiation and determine length of the proliferating columns of chondrocytes - also determine when chondrocytes enter hypertrophy
27
how does the Ihh/PTHrP regulatory loop control chondrocyte differentiation kinetics (mechanism)
- PTHrP produced by early proliferative chondrocytes near ends of bone/growth plate - this acts on PTH1R receptor in late proliferating/prehypertrophic chondrocytes to keep them proliferating -when chondrocytes are far enough away from source they are no longer stimulated by PTHrP -> stop proliferating -> become prehypertrophic -> synthesize Ihh - Ihh stimulates chondrocyte proliferation - Ihh diffuses to ends of bones and acts on early proliferating cells stimulating them to produce more PTHrP - Ihh also induces periosteal cells to form the mineralized bone collar
28
what does the feedback loop of chondrocyte differentiation kinetics ensure
once cells enter hypertrophy they produce Ihh and PTHrP to ensure proliferation of a continual supply of chondrocytes to replace them
29
what is FGF signaling a critical regulatory for
chondrocyte proliferation/differentiation
30
how many FGF genes are there and how many FDF receptor genes
23 FGF genes and 4 FGF receptor genes
31
what is FGFR3 important in and where is it expressed
important additional regulatory step that limits chondrocyte proliferation and expressed in proliferating/prehypertrophic chondrocytes
32
what does FGFR3 suppress
Ihh
33
where is type 2 collagen found
major fibrillar collagen in cartilage, vitreous humor, and inner ear
34
describe the makeup of type 2 collagen and what gene encodes it
homotrimer of alpha1 (II) chains encoded by COL2A1 gene
35
where is type 10 collagen expressed
hypertrophic cartilage
36
describe the makeup of type 10 collagen and what gene encodes it
homotrimer of alpha1 (X) chains encoded by COL10A1 gene
37
what is the 1st sugar residue in a GAG
amino sugar such as N-acetylglucosamine or N- acetylgalactosamine
38
what is the 2nd sugar residue in a GAG
uronic acid such as glucuronic or iduronic
39
what are the 4 main groups of GAGs
- hyaluronan - chondroitin sulfate and dermatan sulfate - heparan sulfate and heparin - keratan sulfate
40
what are the major proteoglycans in skeletal tissues
aggrecan and versican
41
what are the SLRPs in proteoglycans
decorin, biglycan, fibromodulin, osteoglycin
42
what is aggrecan produced by
proliferating and prehypertrophic chondrocytes
43
what does aggregan core protein have
keratan sulphate and chondroitin sulfate GAG chains
44
what does aggrecan assemble with
hyaluronan
45
what does aggregan regulate
calcification
46
what happens when there are mutations in genes involved with cartilage differentiation and function
chondrodysplasias
47
what is camplomelic dysplasia
rare human syndrome caused by heterozygous loss of function mutation in SOX9
48
what type of disorder is camplomelic dysplasia
autosomal dominant
49
what are the symptoms of camplomelic dysplasia
-hypoplasia of skeletal elements - bowing of limbs - shortened limbs/dislocated hips - underdeveloped shoulder blades - 11 pairs of ribs instead of 12 - clubfoot -ambiguous genitalia - craniofacial abnormalities
50
what happens in impaired PTHrP signaling
late proliferating/prehypertrophic chondrocytes will enter hypertrophy too soon resulting in premature growth plate maturation/skeletal maturation
51
what happens in impaired Ihh signaling
no replacement of proliferating cells once they have gone into hypertrophy resulting in premature closing of the growth plate
52
what do impaired PTFrP and Ihh signaling both lead to
dwarfism
53
what happens in inactivating mutations in PTHrP
brachydactyly type E2 - loss of function
54
what results in inactivating mutations in IHH
-brachydactyly type A1 - acrocapitofemoral dysplasia - loss of function
55
what results in inactivating mutations in PTH1R
-Blomstrand lethal chondrodysplasia -loss of function
56
what results in activating mutations in PTH1R
jansen's metaphyseal chondrodysplasia - gain of function
57
what is the result of activating point mutations in FGFR3
achondroplasia -gain of function
58
what is the most common form of short limbed dwarfism
achondroplasia
59
what type of disorder is achondroplasia
autosomal dominant
60
what are the features of achondroplasia
-short stature with disproportionately short limbs - short fingers/toes - large head/prominent forehead -small midface/flattened nasal bridge - spinal kyphosis or lordosis - varus (bowleg) or valgus ( knock knee) deformities
61
what is the lethal type 2 collagen mutation
achondrogenesis type 2/hypochondrogenesis
62
what are the severe type 2 collagen mutations
spondyloepiphyseal dysplasia, spondyloepimetaphyseal dysplasia congenita, Marshall syndrome
63
what are the mild type 2 collagen mutations
stickler syndrome and early onset osteoarthritis
64
what do mutations causing ACGII- HCG involve
replacement of glycine by bulkier amino acid in triple helical region of alpha1(II) chain
65
what is spondyloepiphyseal dysplasia caused by
mutations in COL2A1 gene
66
what type of disorder is SED
autosomal dominant
67
what are type 10 collagen mutations associated with
Schmid type metaphyseal chondrodysplasia
68
what mutation is associated with Schmid type metaphyseal chondrodysplasia
COL10A1
69
what are symptoms Schmid type metaphyseal chondrodysplasia
short stature, bowing of the long bones, widening/irregularity of growth plates
70
what is the autosomal recessive form of aggrecan associated chondrodysplasias
spondyloepiphyseal dysplasia - aggrecan type
71
what is the autosomal dominant form of aggregan associated chondrodysplasias
spondyloepiphyseal dysplasia - type Kimberly - milder form

Biochem (34 decks)

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