L12: Arthritis

Question 1

What is osteoarthritis (OA)

Answer 1

The slow but progessive loss of ECM and the ‘chondrogenic phenotype’ in cartilage, due to mechanical or degradative damage without obvious reason (primary OA)

Question 2

What can OA result in?

Answer 2

Severe limitation in joint movement, joint deformity, inflammation and severe pain that can reduce quality of life

Question 3

OA is often associated with the formation of new bone, incorrectly loaded. True or false?

Answer 3

True, it can also occur as a result of injury

Question 4

Is OA more collagen or aggrecan dependent?

Answer 4

OA depends on more collagen cleavage, than aggrecan destruction

Question 5

Is OA solely heritable?

Answer 5

No, while 50% of it is heritable its also polygenic and multifactorial

Question 6

Name molecules linked to OA

Answer 6

GDFS growth factors, RuNX2, PTHLH and SMAD3

Question 7

Explain possible treatment/ methods for OA

Answer 7

1. Surgery
2. NSAIDs but they don’t stop disease progession and irreversible ECM loss
3. Identify and target key proteinases
4. Genetic screening may allow susceptible patients to have physiotherapy prior to disease onset

Question 8

What is rheutamoid arthritis (RA)?

Answer 8

Inflammatory (autoimmune) arthritis and more cmmon in younger patients than OA

Question 9

How does RA affect cartilage?

Answer 9

Causes progressive loss of ECM and chondrogenic phenotype in articular cartilage

Question 10

What causes RA?

Answer 10

Immune cell mediated damage (genetic linkage to MHC; HLA-DR4 in particular)
- is polygenic and multifactorial

Question 11

What does RA result in?

Answer 11

Severe limitation in joint movement, deformity,

subclinical inflammation and severe pain that can reduce quality of life§

Question 12

Explain how APCA (anti citrulllinated peptide antibodies) are linked to RA

Answer 12

60% of RA patients have APCAs which are specific for peptides from self Ags that contain citrullinated aas
- but still unclear how/if APCAs are related to ECM pathology

Question 13

What is RA characterised by?

Answer 13

Inflammation of synovium and presence of specific B and CD4 Th cell mediated autoimmunity

Question 14

Explain possible treatment methods for RA

Answer 14

1. NSAIDs but hey don’t stop disease progession and irreversible ECM loss
2. (In 80s TNF-alpha indentified as key target for therapy) Infliximab therapy uses a monoclonal Ab that binds TNF-alpha and blocks its action
3. Rituximab (specific for CD20): a monoclonal Ab that kills B cells, used in patients unresponsive to inflixmab
4. Genetic/ ACPA screening: may allow susceptible patients to be identified earlier, so can have therapy at earlier points