Lecture 11 - Osteoarthritus

Question 1

What are the current treatments for osterioarthritis?

Answer 1

Currently they are focused on symptomatic relief

Question 2

Why is the cross talk of cartilage and subchondral bone important?

Answer 2

Because deterioration of one will lead to damage of the other

Question 3

What do chrondrocytes release?

Answer 3

Cytokines stimulating osteoclastogensis

Question 4

What is osteoarthritis/osteoarthrosis?

Answer 4

It is a very common disease of synovial joints

Question 5

What is osteoarthritis/osteoarthrosis characterised by?

Answer 5

Progressive deterioration and focal erosions

Question 6

What is the osteoarthritis/osteoarthrosis progression histology like?

Answer 6

Loss of glossy apperance, fibrillation and erosion of cartilage and exposure of subchrondral bone

Question 7

What do you use as a marker for lysosomal activity?

Answer 7

Acid phosphatase

Question 8

What does acid phosphatase show?

Answer 8

The degree of severity of the disease which is proportional to the level of degradative enzyme activity

Question 9

What are MMP and ADAMT?

Answer 9

MMP = matrix metalloprotease, ADAMT = A disintegrin and metalloprotease with thrombospondin motif

Question 10

Where are MMPs and ADAMTs released from?

Answer 10

Inflammatory cells and chondrocytes

Question 11

What do natural inhibitors inhibit?

Answer 11

An enzyme activity called TIMPs but there is not enough of them around to inhibit all of the activity

Question 12

What do Arya sulphatases do?

Answer 12

Remove sulphate off the PGs this means they wont hold as much water - taken the charge off.

Question 13

What are catespins?

Answer 13

They are proteases found in lysosomal activity and play a role in degradation

Question 14

What are the enzymes changed that occur in osteoarthritis/osteoarthrosis?

Answer 14

Increased enzyme activity = fast extracellular matrix breakdown.
Degradation fragments will diffuse out of the tissue

Question 15

What can happen when the extracellular matrix breaks down?

Answer 15

Synovial fluid can diffuse in and PGs can come out

Question 16

What happens to collagen when the matrix breaks down?

Answer 16

Collagen is not unsupported as there is no PG underneath them - the collagen will lose its stiffness and the fibres will rupture - causes lesions, splits the cartilage

Question 17

What happens when you have an acute inflammatory response in osteoarthritis/osteoarthrosis?

Answer 17

end up with 10^9 leukocytes which will damage the tissue and release large quantities of lysosomal enzymes.

Question 18

What can be seen after large quantities of lysosomal enzymes are released in acute inflammation of osteoarthritis/osteoarthrosis?

Answer 18

Surface adhering immune complexes can be seen

Question 19

How much bigger are inhibitors than enzymes in acute inflammation of osteoarthritis/osteoarthrosis?

Answer 19

Inhibitors are 100-800mW compared to enzymes which are 20-40

Question 20

What is an example of an acute inflammation inhibitor for osteoarthritis/osteoarthrosis?

Answer 20

Alpha 2 macroglobulins

Question 21

What are immature PGs?

Answer 21

They are less associated with the matrix and more easily degraded, so repair process fails

Question 22

What does a fall in synthetic activity in severe disease mean?

Answer 22

Programmed cell death and lacunae (unfilled space) appear in the tissue

Question 23

What would you see if you examined a new synthesised PG?

Answer 23

A higher chondrocyte sulphate to keratin sulphate

Question 24

What is a Lucunae?

Answer 24

A hole in the tissue where the chondrocytes would have been

Question 25

What should an adult PG have?

Answer 25

It should have more chondrocytes 6 sulphate then 4 and it should have lots of keratin sulphate

Question 26

What is a treatment for OA? osteoarthritis/osteoarthrosis?

Answer 26

Platelet rich plasma contains growth factors and cytokines which can reduce tissue damage and inflammation

Question 27

What PGs replace the damage PG in osteoarthritis/osteoarthrosis?

Answer 27

Foetal ones - which is the wrong type

Question 28

What is another treatment for OA? osteoarthritis/osteoarthrosis?

Answer 28

Intra-articular hyaluronic acid (HA) injections every 3 weeks

Question 29

Where do you get hyaluronic acid from?

Answer 29

Cockerel combs or bacterial fermentation

Question 30

What is reduced in someone who has arthritis?

Answer 30

The size of concentration of HA - it goes through quicker

Question 31

How can you repair damaged cartilage?

Answer 31

Make small tubes of alginate and fill with chondrocytes-culture.
In 1 week cartilage would have formed. Cartilage can be transplanted into the damaged areas

Question 32

What do nano particles do?

Answer 32

They transport drug delivery to chondrocytes

Question 33

What do nano particles need to do?

Answer 33

They must penetrate the cartilage matrix

Question 34

What charge are nonparticles?

Answer 34

They can be positive or negative depending size and composition

Question 35

What happens when you get an inflammatory response in the fluid?

Answer 35

You will get a release of aggregation into the synovial fluid, which will cause an immune response as the aggregates are not recognised as normal

Question 36

What is one way of following disease progression?

Answer 36

Bu using biomarkers

Question 37

What happens when you lose the cartilage?

Answer 37

You will have problems with bone articulating on bone, you can get a lot of damage without knowing you have damage as there are no nerves