Lecture 11 - Osteoarthritus Flashcards
(37 cards)
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
