Lecture 13- Osteoarthritis Flashcards Preview

Mechanisms of human disease > Lecture 13- Osteoarthritis > Flashcards

Flashcards in Lecture 13- Osteoarthritis Deck (22):

What is osteoarthritis?

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


What is the similarities between osteoarthritis and rheumatoid arthritis?

Both forms of arthritis involve cartilage destruction.


What features are unique to osteoarthritis?

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


what features are unique to rheumatoid arthritis?

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


What is the role of articular cartilage in a joint?

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


What is articular cartilage composed off?

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


What is collagen comprised off?

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.


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

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.


What are the behavioural properties of collagen fibrils?

Collagen has lots of tensile strength and elasticity.


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

Type 2 cartilage


What is type 9 collagen fibril?

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


What are glycosaminoglycans?

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).


Which glycosaminoglycans are found on aggrecan?

Chondroitin sulphate, keratan sulphate and hyaluronan


What is aggrecan?

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


What is the primary function of aggrecan?

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.


What is the structure of aggrecan?

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.


How does osteoarthritis affect aggrecan?

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


What is the relationship between aggrecan and type 2 collagen ?

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)


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

ADAMTS-5 degrades aggrecan.


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

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


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

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


Are there cures for osteoarthritis?

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