Cartilage Arthritis Flashcards

1
Q

Which articular joints does arthritis occur in hyaline cartilage breakdown

A

Hip and knee joints

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2
Q

What is osteoarthritis

A

Loss of cartilage ecm and has a chondrogenic phenotype

Induced by mechanical stresses eg injury or without cause

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3
Q

What are oa symptoms

A

Loss of joint movement , joint deformity and inflammation pain

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4
Q

How can bone be seen in wrong areas in joint for oa

A

Ossification deformities

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5
Q

Which 3 ways can you detect oa

A

Genetic test

Examine mmp activity

Examine levels of sox9 which allows chondrocyte production

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6
Q

How would integrin usually cause homeostasis

A

Recognise fragments and cause fak signalling causing change in gene exp

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7
Q

What mimics mechanical stress to induce oa in mice

A

Destabilisation of the medial meniscus in joints (dmm)

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8
Q

Which 2 enzymes were found to reduce ecm in dmm oa mice causing oa

A

Adamts5 (reduced aggrecan stain)

Mmp 13 collagenase

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9
Q

What was found to be more important , mm13 or adamts5

A

Mm 13 showing how important collagen is in the ecm of cartilage

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10
Q

What would happen if you mutated the site where mmp13 and adamts5 cuts

A

The ecm would be restored showing low oa levels in dmm mice

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11
Q

How much of oa is inheritable

A

50%

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12
Q

Oa is polygenic what does this mean

A

Many genes involved

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13
Q

Mmp13 is seen in everyone but not everyone develops oa. Explain

A

Oa is multi factorial eg dependant also on environment

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14
Q

Give the 4 most important genes causing oa

A

Gdf5

Runx2

Pthlh

Smad3

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15
Q

What does gdf5 do

A

It’s in the tgf family which cause ecm synthesis via chondrocyte release of col II and aggrecan , and reduces mmp

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16
Q

What does runx2 do

A

A tf which induces mmp13 collagen breakdown and ossification

17
Q

What does pthlh do

A

Encode for pthrp involved in maintains chondrocytes

18
Q

What does smad3 do

A

Ic signalling protein involved in the tgfb response

19
Q

What are the 3 ways of therapy for oa since there’s no cure

A

NSAIDs to reduce inflammation Made by ecm breakdown

Surgery to replace joints

Genetic screening eg of sox9,smad3,gdf5

20
Q

What is ra classified as

A

Inflammatory autoimmune disease

21
Q

How is ra same as oa

A

Chondrogenic phenotype and ecm loss

22
Q

What MHC II is responsible for ra (more present in ra patients)

A

Hla - dr4

Particular gene hla drb1

23
Q

Are the symptoms the same as oa

A

Yes Eg loss of joint movement and inflammation

24
Q

What is rheumatoid factor rf

A

Auto igm antibody which binds igg via fc portion in RA

25
Q

Is rf present in people without ra

A

Yes in 15%

26
Q

What is acpa

A

Anti citrullinated peptide ab

Auto antibody in ra recognising citrullinated peptides presented on the dr mhcII

27
Q

How many ra patients have acpa

A

60%

28
Q

What environmental fsctor can increase ptm citrullination of peptides and therefore increase ra

A

Smoking

29
Q

Where does inflammation occur in ra

A

Synovium

30
Q

What are synoviocytes

A

Cells in synovium whcih produce matrix

31
Q

How does inflammation in ra start

A

Unknown trigger causes leukocytes to go to synovium

32
Q

What happens after trigger

A

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

33
Q

What type of cytokines can auto T cells in synovium release

A

Tnf a, il 17 if th17 and also il 1

34
Q

What do tnf a and Il 1 do

A

Cause ecm breakdown by inducing synovium fibroblasts to release mmps

35
Q

What does il 17 do

A

Causes rank ligand release which stimulates osteoclasts for the breakdown of bone

36
Q

What type of auto antigens are recognised by auto T cells in ra

A

Collagen or aggrecan

CIA or PGIA

(Presented on hla dr / mhcII)

37
Q

What drug blocks tnf a

A

Infliximab

38
Q

How does rituximab work for ra

A

Depletes B cells via targeting cd20 and kills them

39
Q

What can be screened to identify ra

A

Acpa