Articular cartilage structure function & metabolism in health & disease

Question 1

what are the bones in the knee joint

Answer 1

tibia
fibula
patella (knee cap)
femur

Question 2

what are the ligaments in the knee joint

Answer 2

lateral collateral ligament
cruciate ligaments
medial collateral ligament

Question 3

name the cartilage of the knee joint

Answer 3

articular cartilage
meniscus

Question 4

what the tendons of the knee joint

Answer 4

patella tendon
quadricep tendon
hamstring tendon
iliotibial tendon

Question 5

what is articular cartilage comprised of

Answer 5

collagens
proteoglycans
water

Question 6

what is the biomechanical function of articular cartilage

Answer 6

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

Question 7

describe the morphology of articular cartilage

Answer 7

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

Question 8

how much water is in articular cartilage

Answer 8

water accounts for 65-85% of its wet weight

Question 9

what do chondrocytes do in the AC

Answer 9

they are resident cells and produce collagen, proteoglycan and enzymes

Question 10

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

Answer 10

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

Question 11

what is the main proteoglycan and whats its role

Answer 11

aggrecan is the major proteoglycan and it gives cartilage compressive stiffness

Question 12

what are the morphological layers of chondrocytes

Answer 12

superficial zone
middle (intermediate) zone
deep zone
calcified zone

Question 13

describe the superficial layer of collagen

Answer 13

cells are flat
collagen fibrils are parallel to articular surface

Question 14

describe the intermediate layer of collagen

Answer 14

cells are round
collagen fibrils are diagonal to articular surface

Question 15

describe the deep layer of collagen

Answer 15

cells are round
collagen fibrils are perpendicular to articular surface

Question 16

describe the calcified layer of collagen

Answer 16

cells are round
collagen fibrils are perpendicular to articular surface

Question 17

what do collagen heterotypic fibres do

Answer 17

provide high tensile and shear strength

Question 18

what is the biochemical composition of Aggrecan monomer

Answer 18

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

Question 19

what are aggrecan aggregates composed of

Answer 19

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

Question 20

what is the biomechanical function of glycosamnioglycan chains

Answer 20

glycosaminoglycan chains have negative charges creating strong charge repulsive forces.

Question 21

what does charge repulsion do to proteoglycans

Answer 21

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

Question 22

what is the combined function of collagen and proteoglycans in cartilage

Answer 22

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

Question 23

what is cartilage homeostasis

Answer 23

it is the balance between synthesis and degradation of the ECM

Question 24

what is the major proteinases responsible for matrix turnover in cartilage

Answer 24

metalloproteinases are the major proteinases responsible for matrix turnover

Question 25

cartilage turnover is relatively slow in adults. true or false

Answer 25

true

Question 26

what does collagenases & gelatinases degrade

Answer 26

they degrade collagen fibres

Question 27

what do aggrecanses degrade

Answer 27

they degrade aggrecan

Question 28

what do stromelysins degrade

Answer 28

they degrade non collagenous matrix proteins

Question 29

name two metalloprotenases

Answer 29

- matrix metalloproteinase (MMP) - A disintegrin and metalloproteinase with thrombospondin (ADAMTS)

Question 30

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

Answer 30

it binds zinc at its active site

Question 31

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

Answer 31

it is needed for specific substrate recognition

Question 32

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

Answer 32

it is removed to activate the enzyme

Question 33

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

Answer 33

the degrade triple helical collagens

Question 34

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

Answer 34

they degrade denatured collagens

Question 35

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

Answer 35

they degrade non collagenous matrix proteins (not aggrecan)

Question 36

what are the symptoms of Osteoarthritis

Answer 36

limited movement pain crepitation sensitivity to cold and or damp

Question 37

what are the 2 classifications of osteoarthritis based upon etiology

Answer 37

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

Question 38

what are some of the causes/ risks of OA

Answer 38

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

Question 39

how is OA diagnosed

Answer 39

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

Question 40

what is the main hallmark of OA

Answer 40

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

Question 41

how is aggrecanase activity defined in cartilage metabolism

Answer 41

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

Question 42

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

Answer 42

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

Question 43

what degrades collagen in the late stages of OA

Answer 43

MMPs

Question 44

what does a loss in aggrecan result in

Answer 44

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

Question 45

what does the loss in collagen results in

Answer 45

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

Question 46

collagen loss is irreversible. true or false

Answer 46

true

Question 47

what is the treatment for osteoarthritis

Answer 47

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