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Concepts of disease > Articular cartilage structure function & metabolism in health & disease > Flashcards

Articular cartilage structure function & metabolism in health & disease Flashcards

1
Q

what are the bones in the knee joint

A

tibia
fibula
patella (knee cap)
femur

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2
Q

what are the ligaments in the knee joint

A

lateral collateral ligament
cruciate ligaments
medial collateral ligament

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3
Q

name the cartilage of the knee joint

A

articular cartilage
meniscus

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4
Q

what the tendons of the knee joint

A

patella tendon
quadricep tendon
hamstring tendon
iliotibial tendon

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5
Q

what is articular cartilage comprised of

A

collagens
proteoglycans
water

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6
Q

what is the biomechanical function of articular cartilage

A

the properties of water collagen and proteoglycans allow the tissue to withstands load and provide a near frictionless surface for joint articulation

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7
Q

describe the morphology of articular cartilage

A

it is avascular, aneural, hypocellular. it has no lymphatics and no basement membrane.

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8
Q

how much water is in articular cartilage

A

water accounts for 65-85% of its wet weight

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9
Q

what do chondrocytes do in the AC

A

they are resident cells and produce collagen, proteoglycan and enzymes

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10
Q

what is the main collagen in AC and what is its role

A

type II collagen is the major collagen and provides a cartilaginous framework and tensile strength

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11
Q

what is the main proteoglycan and whats its role

A

aggrecan is the major proteoglycan and it gives cartilage compressive stiffness

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12
Q

what are the morphological layers of chondrocytes

A

superficial zone
middle (intermediate) zone
deep zone
calcified zone

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13
Q

describe the superficial layer of collagen

A

cells are flat
collagen fibrils are parallel to articular surface

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14
Q

describe the intermediate layer of collagen

A

cells are round
collagen fibrils are diagonal to articular surface

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15
Q

describe the deep layer of collagen

A

cells are round
collagen fibrils are perpendicular to articular surface

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16
Q

describe the calcified layer of collagen

A

cells are round
collagen fibrils are perpendicular to articular surface

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17
Q

what do collagen heterotypic fibres do

A

provide high tensile and shear strength

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18
Q

what is the biochemical composition of Aggrecan monomer

A

has a aggrecan protein core
has 100 chondroitin sulphate chains
50 keratan sulphate chains
glycosaminoglycans
G2 domain
interglobular domain (IGD)
hyaluronan binding domain

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19
Q

what are aggrecan aggregates composed of

A

30-50 aggrecan monomers
1 hyaluronan glycosaminoglycan
30-50 link proteins (stabilise the aggrecan interactions which are non-covalent)

20
Q

what is the biomechanical function of glycosamnioglycan chains

A

glycosaminoglycan chains have negative charges creating strong charge repulsive forces.

21
Q

what does charge repulsion do to proteoglycans

A

charge repulsion stiffens proteoglycans in the collagen network and gives cartilage compressive stiffness

22
Q

what is the combined function of collagen and proteoglycans in cartilage

A

collagen provides tensile properties through its fibre networks, the osmotic swelling pressure of the high concentration of aggrecan also contributes to the load bearing properties of cartilage.

aggrecan is immobilised within the matrix by forming supramolecular aggregates with hyaluronan and link proteins

23
Q

what is cartilage homeostasis

A

it is the balance between synthesis and degradation of the ECM

24
Q

what is the major proteinases responsible for matrix turnover in cartilage

A

metalloproteinases are the major proteinases responsible for matrix turnover

25
Q

cartilage turnover is relatively slow in adults. true or false

A

true

26
Q

what does collagenases & gelatinases degrade

A

they degrade collagen fibres

27
Q

what do aggrecanses degrade

A

they degrade aggrecan

28
Q

what do stromelysins degrade

A

they degrade non collagenous matrix proteins

29
Q

name two metalloprotenases

A
  • matrix metalloproteinase (MMP)
  • A disintegrin and metalloproteinase with thrombospondin (ADAMTS)
30
Q

what does the catalytic domain do in the matrix metalloproteinases do in cartilage metabolism

A

it binds zinc at its active site

31
Q

what does the hemopexin domain do in the matrix metalloproteinases do in cartilage metabolism

A

it is needed for specific substrate recognition

32
Q

why is the propeptide removed in the matrix metalloproteinases in cartilage metabolism

A

it is removed to activate the enzyme

33
Q

what do collagenases (MMP-1 & MMP-13) do in the matrix metalloproteinases in cartilage metabolism

A

the degrade triple helical collagens

34
Q

what do gelatinases (MMP-2 &MMP-9) do in the matrix metalloproteinases in cartilage metabolism

A

they degrade denatured collagens

35
Q

what do stromelysins (MMP-3 & MMP-10) do in the matrix metalloproteinases in cartilage metabolism

A

they degrade non collagenous matrix proteins (not aggrecan)

36
Q

what are the symptoms of Osteoarthritis

A

limited movement
pain
crepitation
sensitivity to cold and or damp

37
Q

what are the 2 classifications of osteoarthritis based upon etiology

A
  1. primary - idiopathic (no known cause)
  2. secondary OA (many possible causes such as: post traumatic stress, congenital, malposition, metabolic, endocrine disorder, aseptic osteonecrosis)
38
Q

what are some of the causes/ risks of OA

A

age
sex
heredity
ethnic origin
post menopausal
macrotrauma
repetitive microtrauma
obesity
life style
joint injuries

39
Q

how is OA diagnosed

A

Having a physical exam to check your general health, reflexes, and problem joints. Having images taken of your joint using: X-rays, which can show loss of joint space, bone damage, bone remodeling, and bone spurs. Early joint damage does not usually appear on x-rays

40
Q

what is the main hallmark of OA

A

matrix degradation of the articular cartilage is the main hallmark of the disease and results in loss of tissue function

41
Q

how is aggrecanase activity defined in cartilage metabolism

A

it is defined by the specific cleavage between Glutamate and an Alanine peptide bind in the interglobular domain of aggrecan

42
Q

what does the cleavage between glutamate and an alanine peptide bond in the IGD of aggrecan allow for

A

the cleavage allows the glycosaminoglycan (GAG) attachment domains of aggrecan to be released from the cartilage

43
Q

what degrades collagen in the late stages of OA

A

MMPs

44
Q

what does a loss in aggrecan result in

A

loss of aggrecan results in the loss of glycosaminoglycans and the ability to imbibe water

45
Q

what does the loss in collagen results in

A

loss of collagen results in the breakdown of the framework of cartilage and the tensile strength of the tissue

46
Q

collagen loss is irreversible. true or false

A

true

47
Q

what is the treatment for osteoarthritis

A

steroids
non steroidal anti-inflammatory drugs (NSAIDs) ]anti-cytokine antibodies
neutraceuticals
joint replacement surgery
autologous chondrocyte or mesenchymal repair
future specific drugs to target enzyme activity

Concepts of disease (2 decks)

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