7. Pathogenesis of osteoarthritis - Lesley Robson Flashcards
Give the structure of a synovial joint
Two bones almost meet each other with articular (hyaline) cartilage at the ends (ends of the bones are capped with articular cartilage
Synovial cavity - filled with synovial fluid
Synovial membrane surrounds this
All contained within the articular capsule
What is the function of synovial fluid?
Acts as a lubricant to produce almost frictionless, smooth movement of the joint
What is the articular capsule composed of?
Synovial membrane
Fibrous capsule
What is articular cartilage and where is it found in a joint capsule?
Hyaline cartilage
Caps the ends of bones in synovial joint
What is the function of the articular cartilage? x2
Reduces friction and increase range of movement
Shock absorber
How does hyaline cartilage carry out it’s function?
This provides a smooth, slippery surface at the ends of the bones to reduce friction and to help absorb impacts
Articular hyaline cartilage contains a lot of water (remember that bone is only 5% water) so acts as a sponge and a shock absorber to protect the underlying bone from damage (the weight and force placed on bone is absorbed by the high water content of the hyaline cartilage)
What is a ‘tide mark’?
This is where the articular hyaline cartilage merges with the underlying bone - the cartilage is calcified to merge and this leaves the mark
Why does hyaline cartilage not show on an x-ray and what will be seen instead?
X-ray only images dense tissue i.e. where the calcium salts are - so will show the bone but not the articular cartilage
X-ray will show an apparent space where the articular cartilage actually lies
What are the layers of articular cartilage?
Superficial/tangenital zone Middle/transitional zone Deep/radial zone Tide mark Calcified zone Subchondral zone Cancellous bone
Describe the appearance of the chondrocytes and the collagen orientation of the superficial/tangenital zone
Small, reserve cells - these sit on the surface of the cartilage - these cells are very slowly proliferating - flat and small and in greater density
Collagen fibres are parallel with the surface of the cartilage - nice smooth surface
Describe the appearance of the chondrocytes and the collagen orientation of the medial/transitional zone
These cells increase in size - rounder larger and sparser
Collagen fibres are haphazard and in crisscross arrangement - forms pockets where proteoglycans sit
Describe the appearance of the chondrocytes and the collagen orientation of the deep/radial zone
These cells are larger - hypertrophied and start to produce alkaline vesicles
The chondrocytes stack up as they have proliferated
Cartilage then merges with the underlying bone and there is a tidemark
Collagen fibres are perpendicular to the surface and follows the stacks of the chondrocytes
What are the cells found in cartilage?
Chondrocytes
What is the function of chondrocytes?
These regulate both the synthetic and the catabolic processes
Are continually making more ECM i.e. proteoglycans and also removing the old and damaged proteoglycans
Where are chondrocytes found in the hyaline/articular cartilage?
Each chondrocyte sits in its own lacuna
Chondrocytes have low levels of what organelle and why?
Low number of mitochondria - low energy/O2 consumption
Function of negatively proteoglycans of the articular cartilage is?
Draws water into the articular cartilage from the surrounding synovial fluid
What is the role of the chondrocytes in the superficial zone of cartilage?
These act as reserve cells - these add to the deeper layer when and if required
What is the ECM of cartilage composed of?
80% water
Collagen type II
No neurovasculature or lymphatic vessels
What cells produce the ECM of cartilage?
Chondrocytes
Sit in lacunae
What types of collagen are found in the ECM of cartilage?
Mainly type II
Very small levels of type X - this is found in higher levels in the calcified deeper levels
What collagen type is particularly found in the deeper, calcified layer of the cartilage?
Collagen type X
Where do proteoglycans sit in cartilage?
Transitional layer in pockets produced from the transitional structure of the collagen fibres in this layer
How do proteoglycans exist in cartilage?
What is the collagen type that holds the proteoglycans?
Proteoglycans are present as aggregates - not on their own
Collagen type II holds PGs in place
What is the main characteristic of proteoglycans?
Have negative charge (can trap water)
What is the main proteoglycan in the body?
Aggrecan
What is the main pathology in osteoarthritis (OA)?
Degeneration of the articular (hyaline) cartilage
What are the main joints affected in OA?
The weight bearing joints - the ones under the most stress and strain e.g. knees
How does the bone respond when there is a loss of articular cartilage in OA?
What is the problem with this?
The bone responds by producing more bone in an attempt to heal itself
This rubs and irritates the synovial membrane - irritation, pain, discomfort
What are the risk factors for OA?
Increased age Female gender Racial/ethnic factors Genetics Previous damage Injurious physical activities Obesity (increased strain on joints)
What inflammation occurs in OA?
Local inflammation - release of inflammatory cytokines
Inflammatory cycle
This results in even further reduction of ECM production
Why does OA occur? x3
Age - chondrocytes are getting older and cannot produce as much protein or as good quality protein
Mechanical stress throughout life - increased ROS that chondrocytes are exposed to - not as healthy
Stress induced signals - weakens and reduces quality of the chondrocytes
Lack of what protein causes early onset OA?
What is the protein involved in the genetic aspect of OA?
HMGB2 - High mobility group protein 2
Where is HMGB2 expressed?
Expressed in the superficial zone chondrocytes and supports survival of these cells
What are the three stages of degeneration of the articular cartilage in OA?
Fibrillation
Erosion and cracking
Eburnation
What happens in fibrillation of articular cartilage?
The surface of the cartilage is no longer smooth or flat - becomes frilly with frilly edges to it
What happens in erosion and cracking of articular cartilage?
Slight cracks appear in the cartilage and the synovial fluid thickens
High hydrolic pressure is present on the joint upon movement - fluid is forced into the cracks and causes them to widen further
What happens in eburnation of articular cartilage?
The cracks of the cartilage widen to such a great extent that the cartilage breaks off and there is exposure of the underlying bone
What happens to chondrocytes in OA?
Chondrocyte necrosis - in all layers due to high levels of stress
In which layer is chondrocyte necrosis the most obvious in OA?
In the superficial layer
There is a switch of collagen type II to what type of collagen as the articular cartilage breaks down?
Collage type I - more like fibrocartilage and cannot do its job
What happens to the structure of chondrocytes in the deep layer during degeneration of cartilage in OA?
Remaining chondrocytes in the deep layer proliferate at a very high rate to try and compensate for the loss of superficial layers
High number of chondrocytes - form clusters rather than the organised stacks
Why does articular cartilage thicken and soften in early stages of OA?
There is an initial increase in the water entering the cartilage as the collagen pores get bigger as the fibres start to get damaged - the water is not held and as it leaks out it damages even more collagen fibres
What is the name given to softening cartilage?
Chondromalacia
What happens to the cartilage once it has softens?
Softens and then undergoes fibrillation
What happens to proteoglycans as we age?
As ageing occurs, the proteoglycans get smaller and have less side chains attached to them - cannot hold as much water in the cartilage ECM - water moves in and out and damages the collagen fibres
What is meant by ‘osteophyte’?
Degeneration of artilcular cartilage results in exposed bone - this exposed bone starts to produce even more bone and this is the ‘osteocyte’
What is subchondral sclerosis and why does this occur?
This is thickening of the bone under the cartilage
Sclerosis - pathological thickening of tissue
Why do trabeculae fractures occur in OA?
There is damage to the exposed bone and synovial fluid seeps into the exposed trabeculae structure and causes cracks
Proteoglycans are in which layer of articular cartilage?
Middle transitional zone
Hyaline cartilage has high or low coefficient of friction?
Low
Chondrocytes make up what percentage of the articular cartilage?
<5%
Chondrocytes in the radial/deep layer of articular cartilage have high levels of what two organelles?
Golgi bodies
Endoplasmic reticulum
Function of specialised organelles in the radial layer of articular cartialge is?
Production of proteoglycan side chains
Proteoglycan side chains are positively or negatively charged?
Negatively
Function of negatively charged proteoglycan side chains in articular cartilage?
Draws water out from the synovial fluid into the articular cartilage
Main side chain of proteoglycans in the articular cartilage are?
GAGs polysaccharide units
Two main GAG proteoglycans that attach to aggrecan proteoglycan are?
Keratin sulphate
Chondroitin sulphate
Main protein that composes proteoglycans is?
Hyaluronic acid
Consequences of lack of HMGB2 x3
S of chondrocytes in the superficial zone
Loss of progenitor cells
Reduced synthesis of ECM components
Subchondral bone is exposed in which stage of cartilage degeneration in OA?
Eburnation
As well as osteophytes, what else may form in response to the articular degeneration in OA?
Subchondral cysts
