L6 Osteoarthritis Flashcards
What joints does oa affect
Articulating joints (those with articular cartilage eg hip, hands, knee)
What is between 2 bones covered in articular cartilage
Synovial fluid
What makes up cartilage
Pg, collagen, ecm and peri cellular mateix
What cells are joined by pcm
Chondrocytes (form pg and collagen)
What other sorts of small molecules are there eg for signalling
Growth factors
What does loss of cartilage eg due to impact injury / genetics etc stimulate
Synovitis where it activates inflam cells like macrophages
What do the macrophages then do
Release pro inflam cytokines like TNFa which cause chondrocytes to release more mmp for more breakdown of ecm/cartilage
What is the name for bone spurs which appear and cause pain in oa and restriction of movement
Osteophytes
Why do osteophytes form in oa
Reactivation of endochondral ossification
Why does endochondral ossification occur and what happens
Due to remodelling and loss of cartilage. Chondrocyte proliferation and osteophyte formation to lay down basis for cartilage to bone development
Give the risk factors of oa (more in fr)
Age
Obesity
Injury
Sex
Genetics
What does the fr article suggest about the % in which oa is inherited
40-80%
What 3 main effector genes found in the first gwas 2019
Chst3, smad3 and gdf5
What is chst3
Catalyses sulfation of chondroitin a major pg
What does smad3 do
Signalling downstream of tgfb
Osteoblast development, transcription of other things in cartilage like ecm
What is the importance of gdf5
Chondrocytes development and differentiation (it is part of the tgfb superfamily)
How many rusk allele to do with the actual structure of cartilage are found
6 eg in col2a1,fbn2
not as important as others like the growth factors etc
Why is fubrillin 2 important (found a risk allele for this)
Forms microfibrils In ecm which important for tissue homeostasis and regulating inflammation and bone remodelling
Where are snps usually located in oa risk
Non coding regions eg in enhancer regions I.e changing gene exp
What are eQTLs
Variants which change gene exp patterns
What are meQTLs
Variants which correlate to methylation patterns
Explain about the tgfb risk allele A (further reading) (tgfb important in maintaining cartilage)
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
What does colgalt2 do
Glycosylation of collagen determining correct folding of collagen for integrity in its triple helix
What does the risk allele associated with colgalt2 do
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.
What did the snp in smad3 reduce exp of and increase exp of
Reduced col2a1 but increased mmp13 (breaks down col2) when it’s usually opposite way around.
