Pathogenesis Of OA

Question 1

What type of cartilage is articulate cartilage

Answer 1

Hyaline

Question 2

What provides articulate cartilage with nutrients and hydration

Answer 2

Synovial fluid

Question 3

What merges the deeper layer of articulate cartilage with sub chi drawl bone

Answer 3

Calcified cartilage layer
Tidemark

Question 4

What decides the properties of articulate cartilage

Answer 4

ECM composition

Question 5

Layers of articulate cartilage

Answer 5

Superficial zone
Middle zone
Deep zone
Calcified zone
Subchondral zone
Cancellous bone

Question 6

What layers of articulate cartilage are made up of dead chondrocytes

Answer 6

Calcified and subchondral zones

Question 7

What triggers calcification of chondrocytes at the tide mark of articulate cartilage

Answer 7

pH change

Question 8

How does chondrocyte size, shape, and number vary between the superficial, middle, and deep zones of articulate cartilage

Answer 8

Superficial - flatter, smaller, greater density
Middle - rounder, larger, sparser
Deep - stacked

Question 9

What are chondrocytes found in

Answer 9

Lacunae

Question 10

Why do chondrocytes have low numbers of mitochondria

Answer 10

Low oxygen consumption

Question 11

Why do deep chondrocytes have prominent endoplasmic reticulum and Golgi apparatus

Answer 11

Protein synthesis
Sulphation of mucopolysaccharides

Question 12

What is the main type of collagen in cartilage ECM

Answer 12

Type II

Question 13

What cells make cartilage ECM

Answer 13

Chondroblasts

Question 14

Structure of cartilage ECM

Answer 14

Network of collagen fibrils with pockets containing proteoglycan complexes and chondrocytes

Question 15

Why does cartilage rely on diffusion of nutrients and metabolites

Answer 15

No blood or lymphatic vessels (or nerves)

Question 16

Main 4 types of collagen in cartilage

Answer 16

II IX X XI

Question 17

Is collagen X more common in superficial or deep cartilage

Answer 17

Deep calcified

Question 18

How does collagen fibre orientation differ between superficial, intermediate, and deep cartilage

Answer 18

Superficial - parallel with surface - highest strength + allows gliding
Intermediate - oblique lattice - allows compression
Deep - perpendicular to surface - follows chondrocyte stacks and protect from compression

Question 19

What is the main proteoglycan in cartilage

Answer 19

Aggrecan

Question 20

Components of aggrecan

Answer 20

Core protein
GAG side chains

Question 21

What molecule type are keratin sulphate and chondroitin sulphate

Answer 21

GAG

Question 22

What do aggrecan complexes bind to

Answer 22

Central hylauronic acid filament

Question 23

Features of osteoarthritic joint

Answer 23

Fibrosis
Synovitis
Cartilage failure
Hylauronic acid depolymerised
Osteophytes
Subchondral cysts
Vascular engorgement

Question 24

OA risk genes

Answer 24

GDF5
FRZB
DIO2
COL2A1
Vit D receptor
Oestrogen receptor
IL-1R1
PTGS2/PLA2G4A

Question 25

OA pathophysiology

Answer 25

Chondrocytes damaged -> emergency signal release -> inflammation -> further damage to cartilage, bone, etc

Question 26

Inflammation of the synovial membrane

Answer 26

Synovitis

Question 27

How does Synovitis affect OA

Answer 27

Further inflammatory damage Pain Loss of function

Question 28

How does loss of HMGB2 increase OA

Answer 28

Causes superficial zone cell death, loss of progenitor cells, reduced ECM component synthesis

Question 29

HMGB2 role

Answer 29

Wraps around histones in chondrocytes to protect from damage Supports chondrocyte survival Regulates differentiation of superficial zone cells

Question 30

Where is HMGB2 expressed

Answer 30

Superficial zone chondrocytes

Question 31

3 phases of articulate cartilage degeneration in OA

Answer 31

Fibrillation Erosion and cracking Eburnation

Question 32

Eburnation

Answer 32

Exposed bone becomes polished

Question 33

Microscopic changes in cartilage in OA

Answer 33

Chondrocyte necrosis Isogenic clusters - Focal clumps of chondrocytes from incr proliferation Change from hyaline to fibro - C2 becomes C1 Duplicated tide mark Thinner art cart Thickened calcified cart

Question 34

How does proteoglycan staining appear in OA

Answer 34

Patchy

Question 35

How does increased local proliferation of chondrocytes in OA affect chondrocyte arrangement

Answer 35

Isogenic clusters instead of stacks

Question 36

Chondromalacia

Answer 36

Cartilage softens

Question 37

What causes chondromalacia in OA

Answer 37

Art cart thickens and swells but loss of proteoglycans make it less compressible -> water moves in and out faster-> enzymes released from stressed chondrocytes and synovial membrane cells (MMPs ADAMTs collagenases MAC) -> collagen network breaks down

Question 38

What does chondromalacia progress to

Answer 38

Fibrillation

Question 39

Main characteristic changes to art cart in early OA

Answer 39

Loss of superficial zone Changes to ECM Cell cluster emerge

Question 40

Main characteristics of art cart in late stage OA

Answer 40

Continued ECM loss Chondrocyte hypertrophy

Question 41

Effects of OA on exposed Subchondral bone

Answer 41

Micro fractures Increased osteoblast activity Subchondral sclerosis Focal pressure necrosis Subarticular cycts Vascular engorgement Bone marrow oedema

Question 42

What causes subarticular cycts

Answer 42

Increased osteoclast activity to repair focal pressure necrosis

Question 43

What causes Subchondral sclerosis

Answer 43

Increased osteoblast activity

Question 44

Is damage to Subchondral bone equal over the bone surface

Answer 44

No