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Perio CT Biochem > development of cartilage > Flashcards

development of cartilage Flashcards

1
Q

what is the function of cartilage?

A

provide flexible support and template for bone formation

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2
Q

where can you find cartilage?

A

respiratory system, joints, external ear

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3
Q

what is the composition of cartilage?

A

made of cartilage cells (chondrocytes, chondroblasts, chondroclasts) and ECM

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4
Q

what are found in the extracellular matrix (ECM)?

A
  1. collagen fibers (2,9,10,11)
  2. elastic fibers
  3. ground substance
  4. structural glycoproteins
  5. chondronectin
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5
Q

What is composed of ground substance?

A

proteoglycan aggregates composed of proteoglycans (PGs) and glycosaminoglycans (GAGs)

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6
Q

During embryogenesis what do mesenchymal cells differentiate into?

A

chondroblasts

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7
Q

where do chondrogenic cells reside?

A

inner layer of perichondrium

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8
Q

what do chondroblasts do?

A

deposit initial pericellular matrix on the surface

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9
Q

What is it called when chondroblasts are surrounded by matrix?

A

chondrocytes; these sit in lacunae and can still divide to give interstitial growth

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10
Q

What is isogenous group?

A

division of cells (chondrocytes) that give rise to groups of cells descended from one precursor

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11
Q

What is the chondrogenic layer?

A

the inner cells of perichondrium that differentiate into chondroblasts

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12
Q

Define perichondrium.

A

transitional zone between cartilage and surrounding CT

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13
Q

What is the role of appositional growth?

A

to increase overall size of the cartilage and the initial anlagen (rudimentary basis) of future skeleton.

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14
Q

Describe how the extracellular matrix is compartmentalized.

A

The perichondrium encompasses the isogenous groups, matrices, lacunae and chondrocytes.

The pericellular matrix is circumscribed by the territorial matrix. Territorial matrix is the matrix that is in between each chondrocyte of a isogenous group.

Interterritorial matrix is the matrix in between each isogenous group.

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15
Q

Describe the territorial matrix.

A
  • Surrounds the chondrocytes
  • more proteoglycans than collagen
    type 2 collagen
    high turnover
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16
Q

Describe the interterritorial matrix.

A
  • between isogenous groups
  • more collagen
  • more stable
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17
Q

Explain how collagen and proteoglycans form cartilage.

A
  • Cartilage is collagen embedded in firm, hydrated gel of proteoglycan and structural glycoproteins.
  • collagen is the major matrix protein
  • collagen forms fibrils that aggregate to form fibers and fibers associate into bundles of fibers
  • proteoglycans play a mjor role in the ordering process of collagen;
  • hyaluronic acid (HA) in proteoglycans interact with collagen fibrils
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18
Q

Describe type 2 collagen.

A

a homotrimer of 3 chains encoded by a single gene Col2a1.

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19
Q

What are the four types of collagen in cartilage? Describe type 2 and 10.

A

Type 2, 9, 10, 11 collagen.

Type 2: most abundant and largely cartilage specific

Type X: exclusively expressed in the hypertrophic chondrocyte of hyaline cartilage

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20
Q

Defects or decreased amount of collagen disrupts the development of connective tissue in which diseases? What collagens are mutated to see the se effects?

A

Stickler/Marshal syndrome
Kniest dysplasia

Collagen type 2,9,11

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21
Q

What are characteristics of Kniest?

A

short trunk, shortened arms and legs

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22
Q

What are characteristics of Stickler?

A

loose/flexible joints, scoliosis, early onset arthritis

23
Q

Define proteoglycans.

A

a family of proteoglycans, proteins that contain covalently attached oligosaccharides.

Makes the cartilage strong and flexible and is the property that is unique to cartilage

24
Q

Describe the molecular organization of ECM?

Describe the proteoglycan structure?

A 
ECM organization
Hyaluronan molecule (main fiber where everything attaches to) ;Core proteins attached to hyaluronan molecule by a linker protein; Glycosaminoglycans are the glucose chains connected to the core proteins.

Proteoglycan is the: cartilage linker protein, glycosaminoglycans, and core protein

25
Q

What happens if you knockout the cartilage link protein?

A

perinatal lethal, chondrodysplasia

26
Q

What happens when you knock out aggrecan?

A

perinatal lethal, dwarfism, craniofacial abnormalities

27
Q

What is the function of aggrecan?

A

major structure of macromolecules in cartilage; binds both hyaluronan and link protein

28
Q

what is the function of cartilage link protein?

A

stabilizes aggregates of aggrecan and hyaluronan, giving cartilage its tensile strength and elasticity.

29
Q

What are the clinical characteristics in defects of aggrecans?

A

Craniofacial abnormalites:

macrocephaly, severe midface hypoplasia, asbsent nasal cartilage, prognathism, low set ears

30
Q

What is required for aggrecan to interact with other matrix constiutents?

A

glycosylated aspartic acid

31
Q

What are the two mechanisms of chondrogenesis?

A
  1. interstitial growth: chondrocytes within the cartilage tissue; occurs during early phases of cartilage formation (mitotic duplication of chondrocytes=isogenous groups); occurs along epiphyseal plates of long bones - increase length of long bones and provide cartilage template for endochondral ossification.
  2. appositional growth:
    undifferentiated cells at the surface of the cartilage tissue or perichondrium; increases in cartilage width; incorporates into existing cartilage
32
Q

What enhances the chondrocyte function and synthesis of sulfated glycosaminoglycan?

A

IGF-1, growth hormone, thyroxin, testosterone

33
Q

What decreases the chondrocyte function and synthesis of sulfated glycosaminoglycan?

A

cortisone, hydrocortisone and estrogen

34
Q

the most common dwarfism (achondroplasia/hypochondroplasia) is caused by what mutation?

A

95% caused by Gly 390 Arg mutation in FGFR3

35
Q

What are the effects of missense mutation in FGFR3?

A

leads to constitutive activation of FGF pathway; excessive FGF signaling causes decrease proliferation and hypertrophic maturation of chondrocytes in the growth plate (explains stunted growth of limbs)

36
Q

What is the cause of gigantism and acromegaly?

A

2 possible reasons:

  1. Males that do not make estrogen from androgens due to aromatase p450 deficiency.
  2. Males with inactivating mutation in ERalpha

Note: clinical presentations are similar to that of aromatase deficiency)

37
Q

What role does estrogen have in bone development?

A

required for closure of growth plate

38
Q

What is the composition of hyaline cartilage?

A
  • very few cells
  • ECM collagen type 2 and proteoglycan (aggrecan)
  • ECM mostly composed of H2O (60-80%)
39
Q

What are the general functions of cartilage?

A
  • support soft tissue
  • bear mechanical stress
  • bone movement (sliding area of joints)
  • shock absorber
  • development and growth of long bones (embryonic and post natal)
40
Q

what are the features of cartilage?

A
  • avascular
  • no nerves
  • no lymphatics
41
Q

Why is cartilage limited in size?

A

chondroblast and chondrocytes are only sustained by diffusion of nutrients and metabolites through the aqueous phase of the ECM.

Nutrients are brought by the blood stream to the perichondrium; diffusion to deeply placed cells, transport of water and salts is promoted by intermittent cartilage compression and decompression.

42
Q

How is mature cartilage maintained?

A

chondrocytes

43
Q

How is cartilage homeostasis maintained?

A

mechanical loading and hypoxia

44
Q

Where is repair of cartilage absent?

A

articular cartilage

45
Q

What happens when cartilage is damaged?

A

Regenerates poorly; scar of dense connective tissue often replaces extensively damaged area instead of new cartilage

46
Q

What are the three types of cartilage?

A

hyaline
elastic
fibrocartilage

47
Q

Describe hyaline cartilage.
Is it avascular or vascular?
What cells or collagen does it contain?
Where can you find this cartilage?

A
  • most common, clear appearance of matrix
  • avascular
    surrounded by perichondrium
  • consists of chondrocytes surrounded by territorial and interterritorial matrices containing type 2 collagen interacting with proteoglycans
  • present in the temporary skeleton of embryo, articular cartilage, cartilage of respiratory tract
48
Q

Describe elastic cartilage.
Is it avascular or vascular?
What cells or collagen does it contain?
Where can you find this cartilage?

A

yellowish color due to elastin and elastic fibers

  • avascular
  • surrounded by perichondrium
  • consists of chondrocytes surrounded by territorial and interterritorial matrices containing type 2 collagen interacting with proteoglycans and elastic fibers.
  • Present in the external ear, epiglottis, auditory tube
49
Q

Describe fibrocartilage.
Is it avascular or vascular?
What cells or collagen does it contain?
Where can you find this cartilage?

A

sandwich between dense CT and hyaline cartilage;

  • generally avascular
  • lacks perichondrium
  • consists of chondrocytes and fibroblasts surrounded by type 1 collagen and less rigid ECM
  • considered an intermediate tissue between hyaline cartilage and dense fibrous tissue
  • present in the mandible, articular disks of the knee, intervertebral disks and pubic symphysis
50
Q

Describe articular cartilage.
Is it avascular or vascular?
What cells or collagen does it contain?

A
  • Avascular
  • Lacks perichondrium
  • Aneural, alymphatic
  • Nourished by blood vessels from sub chondral bone and synovial fluid.
  • Type 2 collagen, chondrocytes, proteoglycans, ECM, high water content
51
Q

What is the most common degenerative disease of the musculoskeletal system?

A

Osteoarthritis; affects 60-85% of population

52
Q

What is the earliest signs of osteoarthritis?

What is the later signs of osteoarthritis?

A

Earliest: decrease in proteoglycan content
Later: chondrocyte death

53
Q

What is SOX9 responsible for?

A

chondrocyte differentiation and cartilage formation

54
Q

What results in SOX9 haploinsufficiency?

A

lethal skeletal malformation syndrome and XY sex reversal

Perio CT Biochem (6 decks)

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