Cartilage Arthritis Flashcards
Which articular joints does arthritis occur in hyaline cartilage breakdown
Hip and knee joints
What is osteoarthritis
Loss of cartilage ecm and has a chondrogenic phenotype
Induced by mechanical stresses eg injury or without cause
What are oa symptoms
Loss of joint movement , joint deformity and inflammation pain
How can bone be seen in wrong areas in joint for oa
Ossification deformities
Which 3 ways can you detect oa
Genetic test
Examine mmp activity
Examine levels of sox9 which allows chondrocyte production
How would integrin usually cause homeostasis
Recognise fragments and cause fak signalling causing change in gene exp
What mimics mechanical stress to induce oa in mice
Destabilisation of the medial meniscus in joints (dmm)
Which 2 enzymes were found to reduce ecm in dmm oa mice causing oa
Adamts5 (reduced aggrecan stain)
Mmp 13 collagenase
What was found to be more important , mm13 or adamts5
Mm 13 showing how important collagen is in the ecm of cartilage
What would happen if you mutated the site where mmp13 and adamts5 cuts
The ecm would be restored showing low oa levels in dmm mice
How much of oa is inheritable
50%
Oa is polygenic what does this mean
Many genes involved
Mmp13 is seen in everyone but not everyone develops oa. Explain
Oa is multi factorial eg dependant also on environment
Give the 4 most important genes causing oa
Gdf5
Runx2
Pthlh
Smad3
What does gdf5 do
It’s in the tgf family which cause ecm synthesis via chondrocyte release of col II and aggrecan , and reduces mmp
What does runx2 do
A tf which induces mmp13 collagen breakdown and ossification
What does pthlh do
Encode for pthrp involved in maintains chondrocytes
What does smad3 do
Ic signalling protein involved in the tgfb response
What are the 3 ways of therapy for oa since there’s no cure
NSAIDs to reduce inflammation Made by ecm breakdown
Surgery to replace joints
Genetic screening eg of sox9,smad3,gdf5
What is ra classified as
Inflammatory autoimmune disease
How is ra same as oa
Chondrogenic phenotype and ecm loss
What MHC II is responsible for ra (more present in ra patients)
Hla - dr4
Particular gene hla drb1
Are the symptoms the same as oa
Yes Eg loss of joint movement and inflammation
What is rheumatoid factor rf
Auto igm antibody which binds igg via fc portion in RA
Is rf present in people without ra
Yes in 15%
What is acpa
Anti citrullinated peptide ab
Auto antibody in ra recognising citrullinated peptides presented on the dr mhcII
How many ra patients have acpa
60%
What environmental fsctor can increase ptm citrullination of peptides and therefore increase ra
Smoking
Where does inflammation occur in ra
Synovium
What are synoviocytes
Cells in synovium whcih produce matrix
How does inflammation in ra start
Unknown trigger causes leukocytes to go to synovium
What happens after trigger
Auto reactive T cells eg to citrullinated peltides on MHC hla dr
Get activated and then can also release cytokines, activate auto B cells to produce arthritogenic antibodies
What type of cytokines can auto T cells in synovium release
Tnf a, il 17 if th17 and also il 1
What do tnf a and Il 1 do
Cause ecm breakdown by inducing synovium fibroblasts to release mmps
What does il 17 do
Causes rank ligand release which stimulates osteoclasts for the breakdown of bone
What type of auto antigens are recognised by auto T cells in ra
Collagen or aggrecan
CIA or PGIA
(Presented on hla dr / mhcII)
What drug blocks tnf a
Infliximab
How does rituximab work for ra
Depletes B cells via targeting cd20 and kills them
What can be screened to identify ra
Acpa
