Cartilage ageing

Question 1

Differentiate OA from rheumatoid arthritis

Answer 1

• OA: mild synovitis, main mediators are IL-1b and TNFa

- RHEUMATOID ARTHRITIS: inflamed synovium, IL-1B and TGF-B main mediators

Question 2

Cause - OA

Answer 2

• hard to determine as chronic disease
• humans - mostly idiopathic
• animals - mostly secondary

Question 3

How many injuries in horses relate to injuries/degeneration of teh cartilage?

Answer 3

• about 12%
• MCP 7%
• PIP 4%
• DIP 1%

Question 4

What is the prevalence of OA in canines?

Answer 4

• 20% in adults > 1yo

- 80% geriatric (>8yo)

Question 5

Which dogs is OA common in?

Answer 5

• greyhounds
• large breed dogs
• chondrodysplasia
• osteochondrosis or OCD

Question 6

Which breed has high frequency of lumbosacral disk degeneration?

Answer 6

GSDs (d/t large difference in facet joint angles at L6-L7 and L7-S1)

Question 7

Prevalence - OA in cats

Answer 7

• common radiographic finding in older cats

- prevalence about 90% in appendicular joints

Question 8

What disease are pigs prone to?

Answer 8

OCD

Question 9

List types of cartilage degeneration

Answer 9

• fibrillation
• fissures
• erosion
• eburnation (an ivory-like reaction of bone)

Question 10

Define ageing

Answer 10

progressive loss of physiological functions (fitness and reproduction) that increases the probability of death

Question 11

What are the theories of ageing?

Answer 11

• EVOLUTIONARY (disposable soma, others)
• MOLECULAR (error catastrophie, others)
• CELLULAR (senescence, apoptosis, wear and tear, free radicals)
• SYSTEMIC (neuroendocrine, immunologic

Question 12

Outline disposable soma theory

Answer 12

natural selection tunes the life hx of an organism so that sufficient resources are invested in maintaining the repair mechanisms that prevent ageing until the organism has reproduced. animals need to balance repair and energy resources

Question 13

What is the stochastic theory of ageing?

Answer 13

= error catastrophe

• random events at the cellular and molecular level that drive the ageing process
• damage is the inevitable consequence of the interaction b/w organism and its environemtn
• cellular defense network evolved to protect

Question 14

Cartilage - function - 6

Answer 14

• template for bone growth (foetal development)
• resists compression (weight bearing)
• resilience
• support
• flexibility
• lubrication and movement at diarthrodial joints

Question 15

Main components of hyaline ECM

Answer 15

• Collagen 2
• PGs mostly aggrecan
• water
• smaller amounts of other collagens and proteins (function, matrix assembly and homeostasis)

Question 16

Why is cartilage bad at repairing? 3

Answer 16

• avascular
• aneural
• low cell density

Question 17

Outline swelling pressure in cartilage

Answer 17

• bisphasic system (solid + liquid)
• 70% water is bound to PGs
• reversible deformation

Question 18

Function - collagen

Answer 18

fibrillar organisation, mechanical resilience. Increasing the collagen content increases the cartilage stiffness. In OA, the disruption in the collagen fibres decreases the strength of the solid matrix.

Question 19

Function -aggrecan

Answer 19

hydration and compressive resilience

Question 20

How does normal cartilage end up as OA cartilage?

Answer 20

Homeostatic imbalance b/w anabolic (decreased) and catabolic (increased) capabilities of chondrocytes coupled with a poor capacity of catilage to repair (avascular so no new incoming supply of regenerative SCs)

Question 21

Is OA a classical inflammatory arthropathy?

Answer 21

• NOT a classical inflammatory arthropathy - few neutrophils in the synovial fluid, absence of systemic manifestations of inflammmation, but activates BCs and TCs are increased (source of IL-1B and TNF-a).
• Synovium inflammation present (probably a secondary response to degradation products)

Question 22

OA - risk factors

Answer 22

• age
• genetic (includes male/female bias)
• environment
• mechanical trauma

Question 23

How is cellularity affected by age?

Answer 23

decreases with advanced age - can decrease by 50% in femoral condule b/w 20 and 90 years of age. Thus fewer cells to maintain ECM and fewer stem (progenitor) cells for endogenous repair

Question 24

How is ECM affected by increasing age?

Answer 24

increased ECM calcification

Question 25

How is chondrocyte proliferation affected by age?

Answer 25

proliferation reduced: chondrocytes from older patients proliferate less well

Question 26

How much does cartilage thin with age?

Answer 26

normal thinning with age from >10mm to

Question 27

Is cartilage thickness a scale up factor by weight of animal?

Answer 27

No

Question 28

What is articular cartilage thickness related to?

Answer 28

related to the congruence of teh joint surfaces which equalises the stress (load per unit area) in congruent and incongruent joints

Question 29

Describe congruent joint cartilage

Answer 29

the thin cartilage deforms only a small amount, yet the area of congruent surface is sufficiently large to distribute the load and maintain low stress levels

Question 30

Describe incongruent joint cartilage

Answer 30

deformation of the thick cartilage increases the surface area under compression sufficiently to decrease the stress appropriately. If incongruent joint surfaces were covered by thin cartilage, the load per unit area would be excessive. More stress on cartilage and bone

Question 31

Describe 'junk' accumulation with ageing

Answer 31

- proteolytic mediated processing of PGs: increasing polydisperse population, increased MMP1, 3, 13 and ADAMTS-4,-5 - CONSEQUENCES: decrease in fixed charge density d/t loss of PGs, accumulation of 'junk' degraded products, altered activity of cells in response to 'junk' proteins, 'matrikine' activity

Question 32

How is the growth factor response affected by ageing?

Answer 32

- reduced growth factor response - anabolic responses of chondrocytes (human and equine) are diminished to: TGFb, bFGF, IGF-1 - CONSEQUENCES: can drive an homeostatic imbalance - catabolic activity --> anabolic activity - altered cell signalling pathways and receptor levels

Question 33

T/F: OA is NOT an inevitable consequence of ageing

Answer 33

TRUE: - instead, ageing increases the risk of OA - post-trauma OA in the young (humans and athletic animals) supports this

Question 34

Why is ageing of articular cartilage a risk factor for the onset of OA?

Answer 34

- theory of ageing, disposable sma * CELL: senescence, responses to growth factors and cytokines, junk protein accumulation, proteolytic enzymes - thinning - advanced glycation end products (AGEs) - overall: limitations placed on homeostatic mechanisms, functional consequenes are: altered cellular activity, altered ECM, leads to increased mechanical stress to cells, increased susceptibility by other risk factors.