Matrix Degradation X

Question 1

Hyaline Cartilage - components

Answer 1

Fibrillar Matrix

Amorphous, extra fibrillar matrix

Question 2

Fibrillar Matrix

Answer 2

Primarily type II [80% dry weight]

Question 3

Amorphous matrix - made of, fxn

Answer 3

proteoglycans (aggrecan monomers [20%] bound to hyaluronic acid via link proteins)
+ small non-aggregating proteglycans
Hold water in cartilage

Question 4

Fibrillar Mtartix - fxn

Answer 4

Tensile Strength
Hinders expansion of viscoelastic aggrecan component
FLUID FLOW RESISTANCE = COMPRESSION RESISTANCE

Question 5

OA - changes @ gross level

**

Answer 5

Catabolism Mechanism / anabolic mechanism

Cartilage roughened, eroded, eburnation

Question 6

eburnation

Answer 6

wearing and smoothing of the bone

Question 7

OA - changes in bone and other tissues

**

Answer 7

thickened subchondral bone (scelerotic)
bony outgrowths (osteophytes)
Thick synovial fluid (breakdown products)
avascular - no inflammation

Question 8

OA - Synovium changes

**

Answer 8

cell hyperplasia with mononuclear infiltration and edema

Question 9

OA - cartilage changes

**

Answer 9

Chondrocytes undergo phenotypic modulation
low proliferative activity of chondrocytes
apoptotic cell death

Question 10

OA - biochemical changes

**

Answer 10

destablization and looseing of collage network = matrix destruction
anabolism < catabolism
net loss of proteoglycans

Question 11

Aggrecan Turnover - controlled by, time

Answer 11

ADAMTS-5 and ADAMTS-4 and MMP-3 (stomelysin)
both work outside cell at neutral pH
half-life - days/months

Question 12

Collagen - aging

Answer 12

half time about human lifetime

Destablized by MMP-1 and MMP-13 with age

Question 13

Important ECM enzymes

Answer 13

MMP-1 (Intersital collagenases)
MMP-3 (degrade proteglycans)
MMP-8 (degrade type-I collagen and type III)
*MMP-13 - (cleave type II collagen faster that the other collagenases i.e. articular collagenates and growth plates)

Question 14

TIMP - aka, #, fxn

Answer 14

Tissue Inhibitors of MMPs
Four TIMPS
TIMP3 also inhibits ADAMTS-4&5

Question 15

Reactive oxygen metabolites - types, source, effect

**

Answer 15

superoxide anion (O2-), hydrogen peroxide (H2O2), hydroxyl radical(OH-), nitric oxide (NO2)
Most abundant source = phagocytic cells
Cause the cells to sometimes die through apoptosis and sometimes cause them to release proteases that will start to degrade the cartilage

Question 16

Diagnosis of OA

**

Answer 16

clinical history, physical exam, X rays, MRI
Joint aspiration (biomarkers), blood tests to rule out other causes

Question 17

OA Research

Answer 17

Earlier detection
Genetic studies (Inheritance)
Tissue Engineering

Question 18

Tissue Engeneering

Answer 18

Autologous cartilage transplant
donor cartilage transplantation or bio-engineered cartilage transplantation
Stem cell transplantation
Gene therapy

Question 19

Other treatments

**

Answer 19

Exercise, weight loss, NSAIDs (specifically COX-2 inhibitors), nutritional supplements (glocosamine and chondrotin sulfate), Hyaluronic Acid Injection, Total knee replacement

Question 20

Hyaluronic Acid Injection - effects

Answer 20

lubricates and absorbs shock in the joint

can provide long-term pain relief

Question 21

ADAMTS - aka

Answer 21

A Disintegrin and Metalloproteinase with Thrombospondin motifs

Question 22

Collagenases - process

Answer 22

make single cleavage at one site across all three chains in triple helix (MMP-13)
= 3/4 amino frag and 1/4 carboxyl frag
reduced thermal stability = denaturing, degradation by gelatinases (MMPs 2 and MMP 9)