6 - Normal and Abnormal Joints, Pathogenesis of OA

Question 1

What is the anatomy of a synovial joint

Answer 1

Synovial membrane then fibrous capsule which surround synovial fluid

Question 2

Function of synovial fluid

Answer 2

Provides hydration and nutrition to the joint

Allows fricitonless movement

Question 3

What is the articular cartilage and why is it there

Answer 3

Hyaline cartilage which attaches to the end of a bone to reduce friction and absorb impacts

Question 4

What makes the articular cartilage

Answer 4

Chondrocytes

Question 5

The role of articular cartilage

Answer 5

Elastic
Resilient
Acts as a shock absorber

Question 6

What does the ECM of the articular cartilage consist of

Answer 6

Collagen

Proteoglycans

Question 7

What are the characteristics of chondrocytes in the superficial/tangential zone

Answer 7

Flattened
Smaller
Greater in density

Question 8

What are the characteristics of chondrocytes in the Intermediate/transitional zone

Answer 8

Rounder
Larger
Sparser

Question 9

What are the characteristics of chondrocytes in the Deep/Radial zone

Answer 9

Stacked in columns

Most rounded

Question 10

What is the function of chondrocytes

Answer 10

Regulate and establish micro-environment (the ECM)

Question 11

In which layer is there prominent endoplasmic reticulum and golgi apparatus? why?

Answer 11

Deep layer

For protein synthesis and sulphation of mucopolysaccharrides that form proteoglycan side chains

Question 12

What colour stain are proteoglycans and what is their charge

Answer 12

Red
Negative charge
attract water

Question 13

What is the ECM of the articular cartilage made up of

Answer 13

80% water
Collagen Type 2 mainly 
Proteoglycans
Lack of blood + lymph
No nerve supply

Question 14

What does the collagenT2 do in articular cartilage?

Answer 14

Makes pockets filed with proteoglycans

Question 15

What is the function of proteoglycans

Answer 15

Draw water into the cartilage
Regulates compressibility
Water comes out when you move

Question 16

What is the orientation of collagen fibres superficially?

Answer 16

Parallel with the surface
gives highest tensile properties
Allows gliding

Question 17

What is the orientation of collagen fibres intermediately?

Answer 17

Criss-crossed oblique allows compression

Question 18

What is the orientation of collagen fibres Deep?

Answer 18

Perpendicular to surface follow stacks of chondrocytes

Question 19

What is the main collagen type in the cartilage?

Answer 19

Collagen type 2 (90-95%)

Mainly in superficial layers

Question 20

Where is collagen type 10 found in the cartilage?

Answer 20

Calcified, deeper layers

Question 21

Other types of collagen in the cartilage?

Answer 21

2,9, 10, 11

Question 22

Function of collagen in the cartilage

Answer 22

To hold proteoglycans in place

Question 23

What percentage of dry weight is collagen and proteoglycans

Answer 23

Collagen = 40-70%
PG = 15-40%

Question 24

Features of proteoglycans

Answer 24

Highly hydrophillic
Negatively charged
Traps water

Question 25

What is a proteoglycan made up of

Answer 25

Core protein | Glycosaminoglycan side chains

Question 26

What is the core protein in a proteoglycan

Answer 26

Hyaluronan

Question 27

What are GAGs and some examples?

Answer 27

Linear polysaccharides of repeating disaccharide units - Keratin Sulphate (KS) - Chondroitin Sulphate (CS)

Question 28

Risk factors for Osteoarthritis

Answer 28

``` Increasing age Genetics Diet Infection High BMI Physical activity levels ```

Question 29

What causes the pain and loss of function in osteoarthritis

Answer 29

Damage to chondrocytes | Causes proinflammatory cytokines to be released from chondrocytes

Question 30

What is the function of HMGB2

Answer 30

High Mobility Group Protein 2 | - regulates DNA of chondrocytes wrapping around histones

Question 31

Where is HMGB2 expressed and what does it do there

Answer 31

Superficial zone chondrocytes Supports chondrocyte survival regulates specific differentiation status of superficial zone cells (inc progenitor cells)

Question 32

What does loss of HMGB2 cause

Answer 32

Loss of progenitor cells Death of superfical zone reduced synthesis of ECM components

Question 33

3 Phases of degeneration the articular cartilage goes through in osteoarthritis

Answer 33

1) Fibrillation - small cracks on the surface 2) Erosion and cracking 3) Eburnation - complete loss of cartilage, exposed bone becomes polished

Question 34

Microscopic pathology of osteoarthritis

Answer 34

Chondrocyte necrosis Clumps of chondrocytes rather than columns Change from hyaline to fibrocartilage (Type 1 not 2), reduced thickness

Question 35

What occurs biochemically to the cartilage

Answer 35

Collagen broken down Cartilage thickens and swells Loss of proteoglycans so less compressable

Question 36

Why can there be subchondral sclerosis in osteoarthritis

Answer 36

Bone tries to make itself harder to deal with the lack of articular cartilage Also subarticular cysts

Question 37

Treatment for early osteoarthritis

Answer 37

Cartilage stem/progenitor cells (CSPCs) could help regenerate joint resurfacing, o ECM production and chondroprotection