Pathogenesis of Osteoarthritis

Question 1

What is the function of articular cartilage?

Answer 1

To cap the ends of the bone at synovial joints to provide a smooth and slippery surface with a very low coefficient of friction

Question 2

What type of cartilage is articular cartilage?

Answer 2

Hyaline

Question 3

How does articular cartilage merge with the bone?

Answer 3

The deeper layer of the hyaline cartilage merges with a calcified layer (tidemark) that attaches it to the subchondral bone

Question 4

What are five the layers of articular cartilage?

Answer 4

Superficial (tangential) zone
Middle/intermediate/transitional zone
Deep/radial zone
Tide mark
Calcified zone 
(BONE)

Question 5

Describe the chondrocytes in the superficial layer of articular cartilage

Answer 5

Flatter, smaller and in greater density

Question 6

Describe the chondrocytes in the middle/intermediate layer of articular cartilage

Answer 6

The cells are rounder, larger and sparser

Question 7

Describe the chondrocytes in the deep layer of articular cartilage

Answer 7

The chondrocytes are stacked as they have proliferated

Question 8

Why layer of articular cartilage is mainly responsible for the production of proteoglycans?

Answer 8

Deep layer - have prominent ER and golgi apparatus (responsible for protein synthesis and sulphating of mucopolysaccharides which form the proteoglycans)

Question 9

Describe the composition of the extracellular matrix in cartilage

Answer 9

80% water, type II collagen and proteoglycans (hyaluronic acid core protein with GAG side chains)

Question 10

Describe the structure of proteoglycans

Answer 10

Consist of a core protein (e.g. hyaluronic acid) with GAG side chains (e.g. keratin sulphate or chondroitin sulphate)

Question 11

Name an example of a proteoglycan

Answer 11

Aggrecan

Question 12

How does articular cartilage derive it’s nutrients?

Answer 12

It is avascular, lacking blood and lymphatic vessels, and therefore the survival and synthetic activity of the cartilage depends upon the diffusion of nutrients through the matrix (which is facilitated by the lack of a basement membrane in the synovium)

Question 13

What surrounds each chondrocyte?

Answer 13

Lacunae (lie in a puddle-like structure)

Question 14

What is a lacuna?

Answer 14

A pool that surrounds each chondrocyte in cartilage

Question 15

Why do chondrocytes have a low number of mitochondria?

Answer 15

They aren’t very metabolically active, they only divide in response to injury or disease

Question 16

Describe the orientation of collagen fibres in the superficial layer of articular cartilage

Answer 16

Collagen lies parallel with the surface of cartilage to allow gliding

Question 17

Describe the orientation of collagen fibres in the middle layer of articular cartilage

Answer 17

Collagen has a criss-cross, oblique organisation to allow for compression

Question 18

Describe the orientation of collagen fibres in the deep layer of articular cartilage

Answer 18

Collagen lies perpendicular to the surface

Question 19

What is the most prominent type of collagen present in articular cartilage?

Answer 19

Type II

Question 20

Where is type II collagen most dense in articular cartilage?

Answer 20

Superficial layer

Question 21

Where is type X collagen most dense in articular cartilage?

Answer 21

Calcified deep layer

Question 22

What types of collagen are present in articular cartilage?

Answer 22

Type II, IX, X and XI

Mainly II, with a little X

Question 23

What are the risk factors for osteoarthritis?

Answer 23

Intrinsic joint vulnerability, systemic factors and use factors (obesity/injurious physical activity)

Question 24

Outline the genetic basis that may influence the pathogenesis of osteoarthritis

Answer 24

HMGB2 (high mobility group protein 2) - expressed by chondrocytes in the superficial zone to support chondrocyte survival and differentiation of progenitor cells, therefore loss of this expression/gene leads to superficial zone cell death and loss of progenitor cells –> reduced synthesis of components for the ECM

Question 25

What gene is associated with the pathogenesis of osteoarthritis?

Answer 25

HMGB2

Question 26

What are the macroscopic three phases of degeneration in osteoarthritis?

Answer 26

Fibrillation, erosion and cracking and eburnation (complete loss of cartilage)

Question 27

What are the microscopic changes that occur in osteoarthritis?

Answer 27

Chondrocyte necrosis (more marked in superficial layer with focal clumps of proliferation; form isogenic clusters), there is a change from type II to type I collagen which leads to the formation of a second tidemark (visible on histology) with a thickening of the calcified cartilage (which merges with the subchondral bone)

Question 28

What are the biochemical changes seen in osteoarthritis?

Answer 28

> Articular cartilage thickens and swells due to increased water uptake
There is loss of proteoglycans
Collagen network begins to be broken down (due to release of MMPs, collagenases and ADAMTs from stressed synovial membrane cells and chondrocytes)

Question 29

Provide an overview of the pathogenesis of osteoarthritis

Answer 29

Something causes increased expression of degradative enzymes in chondrocytes –> greater breakdown to deposition of cartilage. Gradual change from type II to type I cartilage and there is swelling. Chondrocytes attempt to repair and become ‘stressed’ which leads to the release of MMPs, collagenases and ADAMTs which then breakdown the collagen network –> cartilage breakdown. Eventually the cartilage will fibrillate (crack) and ‘joint mice’ fragments come off, which are engulfed by type A synoviocytes –> inflammatory mediators are attracted –> further degradation –> until there is complete eburnation (Bone on bone).

Question 30

How may osteoarthritis affect the subchondral bone?

Answer 30

As the articular cartilage is eroded, the underlying bone is exposed which can lead to micro fractures of the trabecular that cause osteoblasts to form new bone –> subchondral stenosis