Matrix Degradation X Flashcards Preview

Undeleted > Matrix Degradation X > Flashcards

Flashcards in Matrix Degradation X Deck (22):
1

Hyaline Cartilage - components

Fibrillar Matrix
Amorphous, extra fibrillar matrix

2

Fibrillar Matrix

Primarily type II [80% dry weight]

3

Amorphous matrix - made of, fxn

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

4

Fibrillar Mtartix - fxn

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

5

OA - changes @ gross level
**

Catabolism Mechanism / anabolic mechanism
Cartilage roughened, eroded, eburnation

6

eburnation

wearing and smoothing of the bone

7

OA - changes in bone and other tissues
**

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

8

OA - Synovium changes
**

cell hyperplasia with mononuclear infiltration and edema

9

OA - cartilage changes
**

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

10

OA - biochemical changes
**

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

11

Aggrecan Turnover - controlled by, time

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

12

Collagen - aging

half time about human lifetime
Destablized by MMP-1 and MMP-13 with age

13

Important ECM enzymes

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)

14

TIMP - aka, #, fxn

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

15

Reactive oxygen metabolites - types, source, effect
**

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

16

Diagnosis of OA
**

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

17

OA Research

Earlier detection
Genetic studies (Inheritance)
Tissue Engineering

18

Tissue Engeneering

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

19

Other treatments
**

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

20

Hyaluronic Acid Injection - effects

lubricates and absorbs shock in the joint
can provide long-term pain relief

21

ADAMTS - aka

A Disintegrin and Metalloproteinase with Thrombospondin motifs

22

Collagenases - process

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)