L6 Osteoarthritis

Question 1

What joints does oa affect

Answer 1

Articulating joints (those with articular cartilage eg hip, hands, knee)

Question 2

What is between 2 bones covered in articular cartilage

Answer 2

Synovial fluid

Question 3

What makes up cartilage

Answer 3

Pg, collagen, ecm and peri cellular mateix

Question 4

What cells are joined by pcm

Answer 4

Chondrocytes (form pg and collagen)

Question 5

What other sorts of small molecules are there eg for signalling

Answer 5

Growth factors

Question 6

What does loss of cartilage eg due to impact injury / genetics etc stimulate

Answer 6

Synovitis where it activates inflam cells like macrophages

Question 7

What do the macrophages then do

Answer 7

Release pro inflam cytokines like TNFa which cause chondrocytes to release more mmp for more breakdown of ecm/cartilage

Question 8

What is the name for bone spurs which appear and cause pain in oa and restriction of movement

Answer 8

Osteophytes

Question 9

Why do osteophytes form in oa

Answer 9

Reactivation of endochondral ossification

Question 10

Why does endochondral ossification occur and what happens

Answer 10

Due to remodelling and loss of cartilage. Chondrocyte proliferation and osteophyte formation to lay down basis for cartilage to bone development

Question 11

Give the risk factors of oa (more in fr)

Answer 11

Age
Obesity
Injury
Sex
Genetics

Question 12

What does the fr article suggest about the % in which oa is inherited

Answer 12

40-80%

Question 13

What 3 main effector genes found in the first gwas 2019

Answer 13

Chst3, smad3 and gdf5

Question 14

What is chst3

Answer 14

Catalyses sulfation of chondroitin a major pg

Question 15

What does smad3 do

Answer 15

Signalling downstream of tgfb

Osteoblast development, transcription of other things in cartilage like ecm

Question 16

What is the importance of gdf5

Answer 16

Chondrocytes development and differentiation (it is part of the tgfb superfamily)

Question 17

How many rusk allele to do with the actual structure of cartilage are found

Answer 17

6 eg in col2a1,fbn2

not as important as others like the growth factors etc

Question 18

Why is fubrillin 2 important (found a risk allele for this)

Answer 18

Forms microfibrils In ecm which important for tissue homeostasis and regulating inflammation and bone remodelling

Question 19

Where are snps usually located in oa risk

Answer 19

Non coding regions eg in enhancer regions I.e changing gene exp

Question 20

What are eQTLs

Answer 20

Variants which change gene exp patterns

Question 21

What are meQTLs

Answer 21

Variants which correlate to methylation patterns

Question 22

Explain about the tgfb risk allele A (further reading) (tgfb important in maintaining cartilage)

Answer 22

A found to have reduced protein complex binding which could have txn activity. Only binds sp1 which has low txn activity and also it recruits dnmts which hypermethylste cpgs in enhance region further reducing gene exp

Question 23

What does colgalt2 do

Answer 23

Glycosylation of collagen determining correct folding of collagen for integrity in its triple helix

Question 24

What does the risk allele associated with colgalt2 do

Answer 24

Allele c is found to reduce methylation of the enhancer region at 3 cpgs. This correlates to the gene exp being increased of colgalt2. This could affect folding of collagen and reduce its integrity.

Question 25

What did the snp in smad3 reduce exp of and increase exp of

Answer 25

Reduced col2a1 but increased mmp13 (breaks down col2) when it’s usually opposite way around.