Articular cartilage structure function & metabolism in health & disease Flashcards
what are the bones in the knee joint
tibia
fibula
patella (knee cap)
femur
what are the ligaments in the knee joint
lateral collateral ligament
cruciate ligaments
medial collateral ligament
name the cartilage of the knee joint
articular cartilage
meniscus
what the tendons of the knee joint
patella tendon
quadricep tendon
hamstring tendon
iliotibial tendon
what is articular cartilage comprised of
collagens
proteoglycans
water
what is the biomechanical function of articular cartilage
the properties of water collagen and proteoglycans allow the tissue to withstands load and provide a near frictionless surface for joint articulation
describe the morphology of articular cartilage
it is avascular, aneural, hypocellular. it has no lymphatics and no basement membrane.
how much water is in articular cartilage
water accounts for 65-85% of its wet weight
what do chondrocytes do in the AC
they are resident cells and produce collagen, proteoglycan and enzymes
what is the main collagen in AC and what is its role
type II collagen is the major collagen and provides a cartilaginous framework and tensile strength
what is the main proteoglycan and whats its role
aggrecan is the major proteoglycan and it gives cartilage compressive stiffness
what are the morphological layers of chondrocytes
superficial zone
middle (intermediate) zone
deep zone
calcified zone
describe the superficial layer of collagen
cells are flat
collagen fibrils are parallel to articular surface
describe the intermediate layer of collagen
cells are round
collagen fibrils are diagonal to articular surface
describe the deep layer of collagen
cells are round
collagen fibrils are perpendicular to articular surface
describe the calcified layer of collagen
cells are round
collagen fibrils are perpendicular to articular surface
what do collagen heterotypic fibres do
provide high tensile and shear strength
what is the biochemical composition of Aggrecan monomer
has a aggrecan protein core
has 100 chondroitin sulphate chains
50 keratan sulphate chains
glycosaminoglycans
G2 domain
interglobular domain (IGD)
hyaluronan binding domain
what are aggrecan aggregates composed of
30-50 aggrecan monomers
1 hyaluronan glycosaminoglycan
30-50 link proteins (stabilise the aggrecan interactions which are non-covalent)
what is the biomechanical function of glycosamnioglycan chains
glycosaminoglycan chains have negative charges creating strong charge repulsive forces.
what does charge repulsion do to proteoglycans
charge repulsion stiffens proteoglycans in the collagen network and gives cartilage compressive stiffness
what is the combined function of collagen and proteoglycans in cartilage
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
what is cartilage homeostasis
it is the balance between synthesis and degradation of the ECM
what is the major proteinases responsible for matrix turnover in cartilage
metalloproteinases are the major proteinases responsible for matrix turnover
cartilage turnover is relatively slow in adults. true or false
true
what does collagenases & gelatinases degrade
they degrade collagen fibres
what do aggrecanses degrade
they degrade aggrecan
what do stromelysins degrade
they degrade non collagenous matrix proteins
name two metalloprotenases
- matrix metalloproteinase (MMP)
- A disintegrin and metalloproteinase with thrombospondin (ADAMTS)
what does the catalytic domain do in the matrix metalloproteinases do in cartilage metabolism
it binds zinc at its active site
what does the hemopexin domain do in the matrix metalloproteinases do in cartilage metabolism
it is needed for specific substrate recognition
why is the propeptide removed in the matrix metalloproteinases in cartilage metabolism
it is removed to activate the enzyme
what do collagenases (MMP-1 & MMP-13) do in the matrix metalloproteinases in cartilage metabolism
the degrade triple helical collagens
what do gelatinases (MMP-2 &MMP-9) do in the matrix metalloproteinases in cartilage metabolism
they degrade denatured collagens
what do stromelysins (MMP-3 & MMP-10) do in the matrix metalloproteinases in cartilage metabolism
they degrade non collagenous matrix proteins (not aggrecan)
what are the symptoms of Osteoarthritis
limited movement
pain
crepitation
sensitivity to cold and or damp
what are the 2 classifications of osteoarthritis based upon etiology
- primary - idiopathic (no known cause)
- secondary OA (many possible causes such as: post traumatic stress, congenital, malposition, metabolic, endocrine disorder, aseptic osteonecrosis)
what are some of the causes/ risks of OA
age
sex
heredity
ethnic origin
post menopausal
macrotrauma
repetitive microtrauma
obesity
life style
joint injuries
how is OA diagnosed
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
what is the main hallmark of OA
matrix degradation of the articular cartilage is the main hallmark of the disease and results in loss of tissue function
how is aggrecanase activity defined in cartilage metabolism
it is defined by the specific cleavage between Glutamate and an Alanine peptide bind in the interglobular domain of aggrecan
what does the cleavage between glutamate and an alanine peptide bond in the IGD of aggrecan allow for
the cleavage allows the glycosaminoglycan (GAG) attachment domains of aggrecan to be released from the cartilage
what degrades collagen in the late stages of OA
MMPs
what does a loss in aggrecan result in
loss of aggrecan results in the loss of glycosaminoglycans and the ability to imbibe water
what does the loss in collagen results in
loss of collagen results in the breakdown of the framework of cartilage and the tensile strength of the tissue
collagen loss is irreversible. true or false
true
what is the treatment for osteoarthritis
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
