Osteoarthritis

Question 1

What does dejenerative joint disease/osteoarthritis generally lead to?

Answer 1

structure failure of a synovial joint
pain and disability
erosion of cartilage
osteophyte formation
joint space narrowing

Question 2

What structures are involved in osteoarthritis?

Answer 2

cartilage, synovium, bone, enthesis, tendons, ligaments, muscles, neural, vasculature
in late stage: systemic

Question 3

What drives osteoarthritis?

Answer 3

proinflammatory cytokines

Question 4

What is the difference between idiopathic and secondary OA?

Answer 4

idiopathic: underlying cause not always known but associated with age, mechanical overuse, genetics

secondary: explained by a known medical condition/cause

Question 5

What are the 4 zones of hyaline articular cartilage and what is in their ECM?

Answer 5

superficial: horizontal layer on collagen and chondrocytes
mid: aggrecan/hyaluronan/link protein along with collagen and chondrocytes
deep: vertical version of mid
calcified zone: sub-chondral bone

Question 6

What is the function of cartilage?

Answer 6

dissipation of loads during locomotion
smooth lubrication surface between joints

Question 7

What are the forces acting on cartilage?

Answer 7

dynamic compression
dynamic shear
static compression

Question 8

What are the general characteristics of articular cartilage?

Answer 8

chondrocytes: synthesise matrix, reside within lacunae
avascular: no new supply of cells, poor capacity to repair when injured, nutrient supply is via the vascularised subchondral bone and the synovial surface
aneural
ECM: major component in collagen type 2 for resilience and tensile properties, contains proteoglycans = ++ water
load bearing: experiences various types of loads, reversible deformation, dissipates load across a larger area to reduce impact trauma

Question 9

What are normal age related changes regarding chondrocytes?

Answer 9

depletion in numbers
senescense (stress-induced)
reduced anabolic activity and response to growth factors and cytokines
increased catabolic activity (more responsive to proinflammatory cytokines, increase in matrix metalloproteinases)
mesenchymal stem cells (depletion of local population)

Question 10

What is the consequence of depleting chrondrocyte numbers?

Answer 10

effect on homeostasis

Question 11

What is the consequence of chondrocyte senescence?

Answer 11

promote inflammation

Question 12

What is the consequence of reduced anabolic activity of chondrocytes?

Answer 12

altered homeostasis

Question 13

What are the consequences for increased catabolic activity of chondrocytes?

Answer 13

altered homeostasis and reduced hydration of the ECM

Question 14

What is the consequence of depleting numbers of mesenchymal stem cells?

Answer 14

impact on differentiation and replenishing new chondrocytes, effects repair and homeostasis

Question 15

What are normal age-related changes to ECM?

Answer 15

thinning
mechanical stiffening
accumulation of ECM degradation products
decrease in water component

Question 16

What are the consequences of ECM thinning?

Answer 16

alters loading biomechanics

Question 17

What are the consequences of mechanical stiffening of ECM?

Answer 17

increased cross-links between collagen fibers, stiffens the ECM
alters loading biomechanics and fatigue failure

Question 18

What are the consequences of accumulation of ECM degradation products?

Answer 18

activation of chondrocytes and synovial cells, promote inflammation

Question 19

What are consequences of decreased water content in ECMS?

Answer 19

increased compressive stiffness

Question 20

What is the difference between age related changed and OA?

Answer 20

age-related changes appear to mimic those found in OA but they have very distinct processes

Question 21

What are the risk factors and pathophysiological mechanisms leading to OA?

Answer 21

excess and abnormal mechanical loading
dysregulated cytokine activity
chronic low levels or pro-inflammatory cytokines

absence of systemic manifestations of inflammation

synovium inlammation secondary response to degradation products
synovitis increasingly recognised in early disease

Question 22

What physiological functions of chondrocytes are important for cartilage remodelling?

Answer 22

• balance between several cytokines to maintain anabolic and catabolic activities of the ECM and modulate the activities of other cytokines
• imbalance between anabolic and catabolic mechanism leads to cartilage loss

Question 23

What is IL-1 and its role in OA?

Answer 23

major player in OA with TNF-alpha
produced by chondrocytes and synovial macrophages

up-regulates most proteinases in chondrocytes
makes TNF alpha much more potent

Question 24

What are microscopic changes see in early-stage OA?

Answer 24

cartilage, minor fibrillation in superficial to transition zone
chondrocyte hypertrophy/clustering
subchondral bone mass reduction
synovial thickening and inflammatory cells (lymphocytes) migration

Question 25

What are the microscopic changes in late stage OA?

Answer 25

cartilage, full thickness erosion
apoptosis
subchondral bone sclerosis, osteophytes and cysts
neo-vascular infiltration
synovial thickening, immune cell and neo-vasculature
calcification zone increase

Question 26

What is the point of no-return for reversible changes in OA?

Answer 26

disruption in the collagen network

Question 27

What are the drivers of OA?

Answer 27

cytokines

normally act in concert with other cytokines
highly ordered temporal and spatial sequence
creates a complex network (hard to target)
involved in tissue remodelling

Question 28

How common is OA in the horse?

Answer 28

most common joint disease in horses
53% of thoroughbred suffer lameness and 60% are estimated related to degenerative joint dz

Question 29

What increases odds of OA in horses

Answer 29

high levels of exercise/training at an early age

OA incidence increases with age but is exacerbated with intense or over-exercise (trauma)

Question 30

How common is OA in dogs?

Answer 30

80% of over 8y/o dogs
obese 2.3x more likely
diagnosis usually round 10.5y
more common in greyhounds/large/giant breeds

Question 31

How common is OA in cats?

Answer 31

likely underestiamted
radiographic evidence in 26% of over 12y but 90% including all degenerative joint diseases

Question 32

Is OA linked with osteochondrosis?

Answer 32

OCD does not precede OA in most cases
lesions did not ressemble each other on histology

Question 33

What are the changes related to cartilage thickness in the dog?

Answer 33

ageing leads to some cartilage degeneration and thinning regardless of physical activity in older dogs

Question 34

What makes dogs prone to hip dysplasia?

Answer 34

large breeds, GSD, labrador
overload of a joint and regular cyclical loading on one region of the hip joint
age