7. Pathogenesis of osteoarthritis - Lesley Robson Flashcards

1
Q

Give the structure of a synovial joint

A

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

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2
Q

What is the function of synovial fluid?

A

Acts as a lubricant to produce almost frictionless, smooth movement of the joint

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3
Q

What is the articular capsule composed of?

A

Synovial membrane

Fibrous capsule

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4
Q

What is articular cartilage and where is it found in a joint capsule?

A

Hyaline cartilage

Caps the ends of bones in synovial joint

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5
Q

What is the function of the articular cartilage? x2

A

Reduces friction and increase range of movement

Shock absorber

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6
Q

How does hyaline cartilage carry out it’s function?

A

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)

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7
Q

What is a ‘tide mark’?

A

This is where the articular hyaline cartilage merges with the underlying bone - the cartilage is calcified to merge and this leaves the mark

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8
Q

Why does hyaline cartilage not show on an x-ray and what will be seen instead?

A

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

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9
Q

What are the layers of articular cartilage?

A
Superficial/tangenital zone 
Middle/transitional zone 
Deep/radial zone 
Tide mark 
Calcified zone 
Subchondral zone 
Cancellous bone
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10
Q

Describe the appearance of the chondrocytes and the collagen orientation of the superficial/tangenital zone

A

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

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11
Q

Describe the appearance of the chondrocytes and the collagen orientation of the medial/transitional zone

A

These cells increase in size - rounder larger and sparser

Collagen fibres are haphazard and in crisscross arrangement - forms pockets where proteoglycans sit

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12
Q

Describe the appearance of the chondrocytes and the collagen orientation of the deep/radial zone

A

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

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13
Q

What are the cells found in cartilage?

A

Chondrocytes

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14
Q

What is the function of chondrocytes?

A

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

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15
Q

Where are chondrocytes found in the hyaline/articular cartilage?

A

Each chondrocyte sits in its own lacuna

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16
Q

Chondrocytes have low levels of what organelle and why?

A

Low number of mitochondria - low energy/O2 consumption

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17
Q

Function of negatively proteoglycans of the articular cartilage is?

A

Draws water into the articular cartilage from the surrounding synovial fluid

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18
Q

What is the role of the chondrocytes in the superficial zone of cartilage?

A

These act as reserve cells - these add to the deeper layer when and if required

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19
Q

What is the ECM of cartilage composed of?

A

80% water
Collagen type II

No neurovasculature or lymphatic vessels

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20
Q

What cells produce the ECM of cartilage?

A

Chondrocytes

Sit in lacunae

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21
Q

What types of collagen are found in the ECM of cartilage?

A

Mainly type II

Very small levels of type X - this is found in higher levels in the calcified deeper levels

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22
Q

What collagen type is particularly found in the deeper, calcified layer of the cartilage?

A

Collagen type X

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23
Q

Where do proteoglycans sit in cartilage?

A

Transitional layer in pockets produced from the transitional structure of the collagen fibres in this layer

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24
Q

How do proteoglycans exist in cartilage?

What is the collagen type that holds the proteoglycans?

A

Proteoglycans are present as aggregates - not on their own

Collagen type II holds PGs in place

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25
Q

What is the main characteristic of proteoglycans?

A

Have negative charge (can trap water)

26
Q

What is the main proteoglycan in the body?

A

Aggrecan

27
Q

What is the main pathology in osteoarthritis (OA)?

A

Degeneration of the articular (hyaline) cartilage

28
Q

What are the main joints affected in OA?

A

The weight bearing joints - the ones under the most stress and strain e.g. knees

29
Q

How does the bone respond when there is a loss of articular cartilage in OA?

What is the problem with this?

A

The bone responds by producing more bone in an attempt to heal itself

This rubs and irritates the synovial membrane - irritation, pain, discomfort

30
Q

What are the risk factors for OA?

A
Increased age 
Female gender 
Racial/ethnic factors 
Genetics 
Previous damage  
Injurious physical activities 
Obesity (increased strain on joints)
31
Q

What inflammation occurs in OA?

A

Local inflammation - release of inflammatory cytokines
Inflammatory cycle

This results in even further reduction of ECM production

32
Q

Why does OA occur? x3

A

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

33
Q

Lack of what protein causes early onset OA?

What is the protein involved in the genetic aspect of OA?

A

HMGB2 - High mobility group protein 2

34
Q

Where is HMGB2 expressed?

A

Expressed in the superficial zone chondrocytes and supports survival of these cells

35
Q

What are the three stages of degeneration of the articular cartilage in OA?

A

Fibrillation
Erosion and cracking
Eburnation

36
Q

What happens in fibrillation of articular cartilage?

A

The surface of the cartilage is no longer smooth or flat - becomes frilly with frilly edges to it

37
Q

What happens in erosion and cracking of articular cartilage?

A

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

38
Q

What happens in eburnation of articular cartilage?

A

The cracks of the cartilage widen to such a great extent that the cartilage breaks off and there is exposure of the underlying bone

39
Q

What happens to chondrocytes in OA?

A

Chondrocyte necrosis - in all layers due to high levels of stress

40
Q

In which layer is chondrocyte necrosis the most obvious in OA?

A

In the superficial layer

41
Q

There is a switch of collagen type II to what type of collagen as the articular cartilage breaks down?

A

Collage type I - more like fibrocartilage and cannot do its job

42
Q

What happens to the structure of chondrocytes in the deep layer during degeneration of cartilage in OA?

A

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

43
Q

Why does articular cartilage thicken and soften in early stages of OA?

A

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

44
Q

What is the name given to softening cartilage?

A

Chondromalacia

45
Q

What happens to the cartilage once it has softens?

A

Softens and then undergoes fibrillation

46
Q

What happens to proteoglycans as we age?

A

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

47
Q

What is meant by ‘osteophyte’?

A

Degeneration of artilcular cartilage results in exposed bone - this exposed bone starts to produce even more bone and this is the ‘osteocyte’

48
Q

What is subchondral sclerosis and why does this occur?

A

This is thickening of the bone under the cartilage

Sclerosis - pathological thickening of tissue

49
Q

Why do trabeculae fractures occur in OA?

A

There is damage to the exposed bone and synovial fluid seeps into the exposed trabeculae structure and causes cracks

50
Q

Proteoglycans are in which layer of articular cartilage?

A

Middle transitional zone

51
Q

Hyaline cartilage has high or low coefficient of friction?

A

Low

52
Q

Chondrocytes make up what percentage of the articular cartilage?

A

<5%

53
Q

Chondrocytes in the radial/deep layer of articular cartilage have high levels of what two organelles?

A

Golgi bodies

Endoplasmic reticulum

54
Q

Function of specialised organelles in the radial layer of articular cartialge is?

A

Production of proteoglycan side chains

55
Q

Proteoglycan side chains are positively or negatively charged?

A

Negatively

56
Q

Function of negatively charged proteoglycan side chains in articular cartilage?

A

Draws water out from the synovial fluid into the articular cartilage

57
Q

Main side chain of proteoglycans in the articular cartilage are?

A

GAGs polysaccharide units

58
Q

Two main GAG proteoglycans that attach to aggrecan proteoglycan are?

A

Keratin sulphate

Chondroitin sulphate

59
Q

Main protein that composes proteoglycans is?

A

Hyaluronic acid

60
Q

Consequences of lack of HMGB2 x3

A

S of chondrocytes in the superficial zone
Loss of progenitor cells
Reduced synthesis of ECM components

61
Q

Subchondral bone is exposed in which stage of cartilage degeneration in OA?

A

Eburnation

62
Q

As well as osteophytes, what else may form in response to the articular degeneration in OA?

A

Subchondral cysts