Cartilage ageing Flashcards
Differentiate OA from rheumatoid arthritis
- OA: mild synovitis, main mediators are IL-1b and TNFa
- RHEUMATOID ARTHRITIS: inflamed synovium, IL-1B and TGF-B main mediators
Cause - OA
- hard to determine as chronic disease
- humans - mostly idiopathic
- animals - mostly secondary
How many injuries in horses relate to injuries/degeneration of teh cartilage?
- about 12%
- MCP 7%
- PIP 4%
- DIP 1%
What is the prevalence of OA in canines?
- 20% in adults > 1yo
- 80% geriatric (>8yo)
Which dogs is OA common in?
- greyhounds
- large breed dogs
- chondrodysplasia
- osteochondrosis or OCD
Which breed has high frequency of lumbosacral disk degeneration?
GSDs (d/t large difference in facet joint angles at L6-L7 and L7-S1)
Prevalence - OA in cats
- common radiographic finding in older cats
- prevalence about 90% in appendicular joints
What disease are pigs prone to?
OCD
List types of cartilage degeneration
- fibrillation
- fissures
- erosion
- eburnation (an ivory-like reaction of bone)
Define ageing
progressive loss of physiological functions (fitness and reproduction) that increases the probability of death
What are the theories of ageing?
- EVOLUTIONARY (disposable soma, others)
- MOLECULAR (error catastrophie, others)
- CELLULAR (senescence, apoptosis, wear and tear, free radicals)
- SYSTEMIC (neuroendocrine, immunologic
Outline disposable soma theory
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
What is the stochastic theory of ageing?
= 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
Cartilage - function - 6
- template for bone growth (foetal development)
- resists compression (weight bearing)
- resilience
- support
- flexibility
- lubrication and movement at diarthrodial joints
Main components of hyaline ECM
- Collagen 2
- PGs mostly aggrecan
- water
- smaller amounts of other collagens and proteins (function, matrix assembly and homeostasis)
Why is cartilage bad at repairing? 3
- avascular
- aneural
- low cell density
Outline swelling pressure in cartilage
- bisphasic system (solid + liquid)
- 70% water is bound to PGs
- reversible deformation
Function - collagen
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.
Function -aggrecan
hydration and compressive resilience
How does normal cartilage end up as OA cartilage?
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)
Is OA a classical inflammatory arthropathy?
- 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)
OA - risk factors
- age
- genetic (includes male/female bias)
- environment
- mechanical trauma
How is cellularity affected by age?
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
How is ECM affected by increasing age?
increased ECM calcification
How is chondrocyte proliferation affected by age?
proliferation reduced: chondrocytes from older patients proliferate less well
How much does cartilage thin with age?
normal thinning with age from >10mm to
Is cartilage thickness a scale up factor by weight of animal?
No
What is articular cartilage thickness related to?
related to the congruence of teh joint surfaces which equalises the stress (load per unit area) in congruent and incongruent joints
Describe congruent joint cartilage
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
Describe incongruent joint cartilage
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
Describe ‘junk’ accumulation with ageing
- 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
How is the growth factor response affected by ageing?
- 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
T/F: OA is NOT an inevitable consequence of ageing
TRUE:
- instead, ageing increases the risk of OA
- post-trauma OA in the young (humans and athletic animals) supports this
Why is ageing of articular cartilage a risk factor for the onset of OA?
- 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.
