Lecture 12 - Failure to maintain ECM homeostasis

Question 1

Osteoarthritis:

Answer 1

OA, Mechanical or degradative
Usually slow, but progressive loss of the ECM and the chondrogenic phenotype in in articular cartilage due to mechanical or degradative damage without obvious cause
Can occur as a result of injury
Results in severe limitation in joint movement, joint deformity, inflammation and severe pain that substantially reduces quality of life
Often associated with new bone, incorrectly located, due to the loss of cartilage
Common in elderly patients
OA is inherited

Question 2

Give an example of an animal model to study OA:

Answer 2

Can test a hypothesis/new drugs on an animal model
If you cut the medial meniscus (MM) - a ligament - in mice, you weaken the ECM interaction between the bones, so one bone pushes more on another, so stimulating mechanical damage in the bones of mice, so they will develop OA as a result

Question 3

What does multifactorial mean?

Answer 3

Someone can have the exact same genes as another but have different susceptibilities

Question 4

What are the current therapies for OA?

Answer 4

Surgery, Non-steroid anti-inflammatories, Identify and target key proteinases - ADAMTS-5 and MMP-13, both inhibited by TIMP-3

Question 5

Rheumatoid arthritis:

Answer 5

RA, Inflammatory
More common in younger patients than OA
Progressive loss of ECM and chrondrogenic phenotype in articular cartilage due to immune cell mediate damage
Results in severe limitation in joint movement, joint deformity, inflammation and severe pain that can substantially reduce quality of life
This is an inflammatory disease where as OA leads to inflammation
RA a polygenic, multifactorial disease
RA is an autoimmune

Question 6

What is RF?

Answer 6

Rheumatoid factor (RF) it is an autoantibody, and is in the blood of RA patients
It is an IgM bound to a IgG

Question 7

What can RA progression be increased by?

Answer 7

Smoking, Diet, Overweight

Question 8

What is RA characterised by?

Answer 8

The inflammation of the synovium, the joints end up looking like lymph nodes, ECM and cartilage doesn’t have a blood supply or lymphatics so the immune cells shouldn’t be there
Also by the presence of specific B and CD4 Th cell mediated auto-immunity, TNF-alpha is the key cytokine which is induced to destry the matrix, these cells also produce RANK ligand

Question 9

What is RANK ligand?

Answer 9

A growth factor for osteoclasts which eat cartilage

Question 10

What are the current therapies for RA?

Answer 10

Non-steroidal anti-inflammatory drugs (NSAIDs)