Lecture 13- Osteoarthritis

Question 1

What is osteoarthritis?

Answer 1

It is described as the destruction of articular cartilage and changes in the underlying subchondral bone (osteophytes).

Question 2

What is the similarities between osteoarthritis and rheumatoid arthritis?

Answer 2

Both forms of arthritis involve cartilage destruction.

Question 3

What features are unique to osteoarthritis?

Answer 3

light synovial inflammation, thickening of bone, bone spurs or osteophyte development and cartilage destruction.

Question 4

what features are unique to rheumatoid arthritis?

Answer 4

severe synovial inflammation (due to antibody attack), thinning of bone, erosion of bone and cartilage destruction.

Question 5

What is the role of articular cartilage in a joint?

Answer 5

It provides a smooth, frictionless surface for joint movement and is a weight-bearer and shock absorber.

Question 6

What is articular cartilage composed off?

Answer 6

Mainly water, with a few other proteins like Aggrecan and type 2 collagen.

Question 7

What is collagen comprised off?

Answer 7

Collagen is a fibrillar protein found in mammals. There are three polypeptide alpha chains that are wound into a triple helix. The polypeptide chains have a glycine-X-Y amino acid sequence.

Question 8

Why does collagen have the amino acids Glycine and Proline specifically in its amino acid sequences?

Answer 8

Glycine is the smallest amino acid (only has H as its side group), thus it is compact and fits into the helix. Proline’ side group is on an angle, and so Proline creates the bends of the helix that make the collagen compact.

Question 9

What are the behavioural properties of collagen fibrils?

Answer 9

Collagen has lots of tensile strength and elasticity.

Question 10

What type of cartilage is found in the articular cavity of joints?

Answer 10

Type 2 cartilage

Question 11

What is type 9 collagen fibril?

Answer 11

This is an additional collagen structure that forms projections. These projections are attached to the type 2 collagen fibrils.

Question 12

What are glycosaminoglycans?

Answer 12

These are long polysaccharide chains with special disaccharide units. The disaccharide unit has one sugar molecule with an amine group (amino sugar) and the next sugar has an acid group (uronic acid).

Question 13

Which glycosaminoglycans are found on aggrecan?

Answer 13

Chondroitin sulphate, keratan sulphate and hyaluronan

Question 14

What is aggrecan?

Answer 14

Aggrecan is a protein at its core with lots of proteoglycan extensions coming off it.

Question 15

What is the primary function of aggrecan?

Answer 15

Aggrecan has many sulphate groups on it from the chondroitin sulphate glycosaminoglycan. These sulphate groups make an aggrecan molecule very negatively charged. The negative charges are counteracted in the body with positive charges from cations. These cations form salts that attract a lot of water. So, aggrecan’s job is to attract water into the cartilage.

Question 16

What is the structure of aggrecan?

Answer 16

Aggrecan is a very large, linear protein. It has 3 domains. They are the G1, G2 and G3 domains. The G1 domain is at the tail of the aggrecan and binds to a protein called HA. Together, the HA and G1 proteins form an anchor that hold down the aggrecan and stop it from leaving the cartilage.

Question 17

How does osteoarthritis affect aggrecan?

Answer 17

Osteoarthritis causes aggrecan molecules to leave the cartilage by cutting off the G1/HA complex with enzymes called aggrecanases.

Question 18

What is the relationship between aggrecan and type 2 collagen ?

Answer 18

Aggrecan absorbs and attracts water. The type 2 collagen then forms a fibrous network around the aggrecan molecules. Together they form a weightbearing, mobile pad of tissue. (Refer to Drawstring and balloons diagram)

Question 19

In osteoarthritis, what is the main enzyme responsible for aggrecan degradation?

Answer 19

ADAMTS-5 degrades aggrecan.

Question 20

On an x-ray of an osteoarthritic knee joint, what main feature would be evident to prove the presence of the disease?

Answer 20

Joint space narrowing- the cartilage degradation would mean the bones were touching each other or close.

Question 21

What is the relationship between body weight and health of a joint with regards to osteoarthritis?

Answer 21

An abnormal joint or excessive body weight on their own can cause osteoarthritis.

Question 22

Are there cures for osteoarthritis?

Answer 22

No- just symptom modifiers (help to ease the pain of osteoarthritis). Exercise and weight loss are supported as first line treatments.