MSS Cartilage, Chondrocytes and Osteoarthritis Flashcards
What is the clinical presentation of osteoarthritis?
a
- Cartilage damage
- Patients also have high levels of high signal intensity areas on T2-weighted MRIs called bone marrow lesions
- Underneath the cartilage damage, there is swelling of bone + changes within the bone itself
- If this process continues uncontrolled, there is severe loss of cartilage - may need joint replacement
What are stages of cartilage breakdown during arthritis?
Early OA:
- Smooth surface of cartilage loses integrity - Starts to show fibrillation (small cracks or fissures)
- Chondrocytes begin to die
- Intensity of staining decreases
- ECM decreases
End stage OA:
- Deep fissures or cracks form within cartilage
- Cartilage may be completely worn away, leaving bone exposed
- Few remaining chondrocytes
- Severe depletion of ECM
- Results in significant joint dysfunction and pain
Which proteinases degrade joint tissue?
Collagenases such as MMP3 and MMP13 cleave collagen into 1/4 and 3/4, they also cleave the core protein of aggrecan leading to aggrecan fragment formation
Main enzymes causing the cleavage= aggrecanases. This is reversible, hence why early stage intervention stops disease progression
Later on, MMPs come in + start degradation = irreversible!
( This image shows different enzymes cleave the tissue at different points in time.)
Describe the regulatory factors in cartilage and use this to explain why the cartilage doesn’t recover itself
Many catabolic cytokines are released, if they have ongoing release within the joint itself, it is v hard for anabolic cytokines to continue repair
- imbalance between damage and repair - in OA, it is frustrated repair: anabolic cytokines released to repair areas of damage but they don’t necessarily allow that repair to occur in a sustained effect over a longer period of time
What are the mechanisms of OA joint degradation?
DDR2 collagen receptor is upregulated in OA - Its activation produces MMPs, which degrade cartilage.
TLR4 also produces pro-inflammatory cytokines & MMPs
So inhibiting DDR2 + TLR4=slow disease progression
ECM proteins get broken down, they activate DDR2 and TLR4–>activates proteolytic enzymes–> breakdown cartilage
This can continue in a positive feedback loop by
- mechanical stress
- being overweight
- genetic background
- injury
Describe the genetic conditions associated w rapid OA progression
Stickler’s syndrome - inherited mutation in type II collagen. makes you prone to early OA but also lens defect and connective tissue problems in skin, tendons and other parts of the body
What structures are affected in OA?
Underlying bone is also affected in OA
As well as bone marrow lesions, synovium can also become inflamed
Synovial lining can become inflamed and release inflammatory cytokines and lead to the ongoing activation of pro-inflammatory pathways (PGs, LTs, proteinases)
Describe what you would see in large joint OA
On an X-ray, you may see:
- severe cartilage damage
- joint space narrowing
- subchondral cysts
- sclerosis - thickened area of bone
- cartilage loss - inferred on an x-ray. normal cartilage looks black
What does this show?
Use this diagram to explain ultrasound study on people with hand arthritis
Researchers looked at Power Doppler signals on US which indicates more BF and synovial swelling
Before treatment: increased PD signal
4 weeks post one off steriod injection, the PD signal was gone. This shows steroids reduce hand synovitis .
However we dont use sterioids long term for OA bc of side effects - weight gain, diabetes, hypertension, cataracts, skin thinning, bruising etc
What would you see in an MRI of a knee arthritis?
What happens at the osteochondral junction of someone with RA, someone with no arthritis and someone with OA?
Inflammatory changes in OA?
Synovitis also occurs in OA.
What are the current concepts for OA treatment?
