Cartilage and the chondrocyte Flashcards
1
Q
Athroscopy
A
- normal - very bright, pearly white cartilage
- OA - fibrillation in joint
- can get worse and develop fissures. If it happens in a big chunk of cartilage and gets to the underlying bone, then it becomes unable to repair itself
2
Q
Key features of synovial joint
A
- cartilage is avascular and aneural
- outside the bone and cartilage is a fibrous capsule, fat pads and bursa
- every time we stand/sit down, proprioceptors feed up the spinal cord to brain and make changes to allow us to stay stable
- nociceptors give sensation of arthritic pain
3
Q
Types of arthritis
A
- acute - mono/poly-articular. caused by infection or injury
- chronic - mono/poly-articular. causes - autoimmune (RA), degenrative (OA), other
4
Q
MRI scans of knee
A
- may see dip in cartilage integrity (should be a smooth surface)
- can detect cartilage damage early on using these techniques
- areas of high signal shows bone marrow lesions, swellings inside bone (only seen in MRI)
- bone-cartilage interface becomes indiscrete
5
Q
Cartilage structure
A
- aggrecan (large polymer of proteoglycans) - has a negative charge and so exerts huge osmotic pressure because of sugar side chains, drawing in water to cartilage.
- Hyaluronan tethers aggrecan together
- avascular and aneural (otherwise would be v painful)
- Type 2 collagen lines the articular surface of cartilage (parallel), then goes deeper and forms a framework
- chondrocytes - only cells in cartilage, less than 1% total volume but responsible for making all normal proteins
6
Q
Stages of cartilage breakdown in arthritis
A
- surface of cartilage isnt as smooth as should be, cells start to die and make less of a functioning matrix
- if carries on, you have hardly any matrix, and a lot of chondrocytes have died. lots of deep fissuring and so smooth surface has been lost
- need to protect this joint as damage has become irreversible
7
Q
Collagenases
A
- very active in OA cartilage
- active in different tissues as there is collagen turnover, however usually a slow process (faster in arthritis)
- Collagen DNA usually cleaved in a 3/4 - 1/4 pattern - can use neoepitode Abs to detect the 3/4 part
8
Q
Aggrecan
A
- protein chain with keratin and chondrotin sulfate chains
- 3 globular domains (G1-3)
- 11 known cleavage sites
9
Q
Which proteinases degrade joint tissue?
A
- the early cleavage of cartilage will be cause by aggrecanases ADAM-TS4 and AMA-TS5
- Matrix metalloproteinases then kick in
- once MMPs start, you cannot go back as it starts breaking down the structure of type 2 collagen.
10
Q
Regulatory factors in cartilage
A
- cytokines are released during injury and chronic inflammation
- released by activated synovial cells and act on chondrocytes
- activated to induce proinflammatory signalling cells -> release aggrecanases and proteinases etc
- catabolic, anabolic, anti-catabolic and regulatory (mainly interleukins)
11
Q
Mechanisms of OA joint degradation
A
- once the matrix has been broken down, fragments of the materials and cells can be found
- it has been found that these can interact with complement and receptors on the cells that increase inflammation
- initial injury to cartilage can lead to a loop of further damage which spreads from cartilage to bone
- subchondral bone then becomes swollen and can lead to chronic disease if uncontrolled
12
Q
Radiological signs of OA inflammation
A
- X-ray - joint stage almost completely lost. enlarged subchondral bone. cysts are formed from bone marrow lesions
- power doppler - inflammation in the synovium
13
Q
Delayed gadolinium-enhanced MRI (dGEMRIC)
A
- trialling FGF (and other growth factors) injections into OA joints to try and improve cartilage integrity
- a few weeks after injecting into pt, we inject dye
- dye is taken up and binds to GAG in cartilage
- yellow = intact cartilage
- red = damaged cartilage
14
Q
What happens at the osteochondral junction?
A
- OA - deep fissuring, disruption of interface, cartilage cells dying
- RA - lots of inflammatory cells
15
Q
What factors contribute to the joint pain
A
- Pain sensitivity
- joint damage
- psychosocial characteristics
