Lecture 11 - Osteoarthritus Flashcards
What are the current treatments for osterioarthritis?
Currently they are focused on symptomatic relief
Why is the cross talk of cartilage and subchondral bone important?
Because deterioration of one will lead to damage of the other
What do chrondrocytes release?
Cytokines stimulating osteoclastogensis
What is osteoarthritis/osteoarthrosis?
It is a very common disease of synovial joints
What is osteoarthritis/osteoarthrosis characterised by?
Progressive deterioration and focal erosions
What is the osteoarthritis/osteoarthrosis progression histology like?
Loss of glossy apperance, fibrillation and erosion of cartilage and exposure of subchrondral bone
What do you use as a marker for lysosomal activity?
Acid phosphatase
What does acid phosphatase show?
The degree of severity of the disease which is proportional to the level of degradative enzyme activity
What are MMP and ADAMT?
MMP = matrix metalloprotease, ADAMT = A disintegrin and metalloprotease with thrombospondin motif
Where are MMPs and ADAMTs released from?
Inflammatory cells and chondrocytes
What do natural inhibitors inhibit?
An enzyme activity called TIMPs but there is not enough of them around to inhibit all of the activity
What do Arya sulphatases do?
Remove sulphate off the PGs this means they wont hold as much water - taken the charge off.
What are catespins?
They are proteases found in lysosomal activity and play a role in degradation
What are the enzymes changed that occur in osteoarthritis/osteoarthrosis?
Increased enzyme activity = fast extracellular matrix breakdown.
Degradation fragments will diffuse out of the tissue
What can happen when the extracellular matrix breaks down?
Synovial fluid can diffuse in and PGs can come out
What happens to collagen when the matrix breaks down?
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
What happens when you have an acute inflammatory response in osteoarthritis/osteoarthrosis?
end up with 10^9 leukocytes which will damage the tissue and release large quantities of lysosomal enzymes.
What can be seen after large quantities of lysosomal enzymes are released in acute inflammation of osteoarthritis/osteoarthrosis?
Surface adhering immune complexes can be seen
How much bigger are inhibitors than enzymes in acute inflammation of osteoarthritis/osteoarthrosis?
Inhibitors are 100-800mW compared to enzymes which are 20-40
What is an example of an acute inflammation inhibitor for osteoarthritis/osteoarthrosis?
Alpha 2 macroglobulins
What are immature PGs?
They are less associated with the matrix and more easily degraded, so repair process fails
What does a fall in synthetic activity in severe disease mean?
Programmed cell death and lacunae (unfilled space) appear in the tissue
What would you see if you examined a new synthesised PG?
A higher chondrocyte sulphate to keratin sulphate
What is a Lucunae?
A hole in the tissue where the chondrocytes would have been
What should an adult PG have?
It should have more chondrocytes 6 sulphate then 4 and it should have lots of keratin sulphate
What is a treatment for OA? osteoarthritis/osteoarthrosis?
Platelet rich plasma contains growth factors and cytokines which can reduce tissue damage and inflammation
What PGs replace the damage PG in osteoarthritis/osteoarthrosis?
Foetal ones - which is the wrong type
What is another treatment for OA? osteoarthritis/osteoarthrosis?
Intra-articular hyaluronic acid (HA) injections every 3 weeks
Where do you get hyaluronic acid from?
Cockerel combs or bacterial fermentation
What is reduced in someone who has arthritis?
The size of concentration of HA - it goes through quicker
How can you repair damaged cartilage?
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
What do nano particles do?
They transport drug delivery to chondrocytes
What do nano particles need to do?
They must penetrate the cartilage matrix
What charge are nonparticles?
They can be positive or negative depending size and composition
What happens when you get an inflammatory response in the fluid?
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
What is one way of following disease progression?
Bu using biomarkers
What happens when you lose the cartilage?
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
