Cartilage+OA

Question 1

What fraction of people above 45yrs seek treatment for OA?

Answer 1

1/3
-81% of these have constant pain or functional limitations
-7.5 million working days lost per year in UK
-OA pain is the commonest reason for joint replacement
-USA: predicted 0.5M hip replacements each year by 2030

Question 2

What is the commonest reason for joint replacement?

Answer 2

OA

Question 3

What is shown in this arthroscopy?

Answer 3

A chondral defect

Question 4

What components make up the cartilage ECM and what are 2 of their functions?

Answer 4

Aggrecan(type of proteoglycan)-Resist compression
T2 collagens-High tensile strength
Water

Question 5

Outline the function of the chondrocyte

Answer 5

<5% tissue
Producer and degrader of the cartilage matrix
Highly metabolically active
Exist in relative hypoxia
Interactions with matrix: growth factors, mechano-transduction
No cell division after adolescence

Question 6

Give the 4 layers of hyaline cartilage including the location of the tide mark

Answer 6

Superficial layer
Transitional/Intermediate
Deep/Radial
(Tide mark)
Calcified
——-Bone

Question 7

What type of enzyme breaks down collagen?

Answer 7

Collagenases-A type of metalloproteinase

Question 8

Which metalloproteinase are useful for breaking down collagen?

Answer 8

MMPs-3,11,18

Question 9

What type of molecule is MMP-3?

Answer 9

A stromelysin

Question 10

Outline the structure of aggrecan

Answer 10

Sugar chains off of a protein backbone, attached to hyaluronan, contains 3 major domains
-Branches of keratin sulphate and chondroitin sulphate

Question 11

Where can aggrecan be cleaved and by what?

Answer 11

Matrix metalloproteinases between amino acids 341-342

Aggrecanases between amino acids 373-374

Question 12

What are the intrinsic anabolic/anti-catabolic factors for articular cartilage?

Answer 12

TIMPs (Tissue Inhibitor of Metalloproteinases) 1-4
Growth factors e.g. fibroblast growth factor (FGF-2), Insulin-like growth factor (IGF), Transforming growth factor (TGF)-β, activin A

Question 13

What are the extrinsic anabolic/anti-catabolic factors for articular cartilage?

Answer 13

Hormones e.g. testosterone, estrogen
Some drugs e.g. FGF-18

Question 14

Simply, why does cartilage matrix loss occur?

Answer 14

Excessive degradation compared to repair

Question 15

What part of your knee supports most of the weight?

Answer 15

The medial compartment

Question 16

What occurs if your joints are absent of mechanical load?

Answer 16

You can’t maintain cartilage thickness and turnover, leading to cartilage atrophy

Question 17

How much more load is there through the tibiofemoral joint of the knee compared to standing with:
Walking
Jumping
Running
Climbing stairs

Answer 17

Walking – 2-6 X body weight
Jumping – 7-9 X body weight
Running – 3-8 X body weight
Climbing stairs – 3-10 X body weight

Question 18

Describe the pathogenesis of OA

Answer 18

Inflammation
Repair/remodelling of the cartilage
Pain

Question 19

What occurs to the matrix components of cartilage in OA pathology

Answer 19

Proteoglycan-Fragmented by aggrecanases
Water-Increased by initial swelling, then lost
Collagen-Broken down by collagenases

Question 20

Describe the pathology of EARLY OA

Answer 20

-Loss of proteoglycans
-Fibrillation of tissues

Question 21

Features of established OA that early OA doesn’t have?

Answer 21

Established has:
-Fissuring
-Partial/full thickness cartilage loss
-Osteophytes, bone cysts, synovial inflammation

Question 22

What are the risk factors for OA?

Answer 22

Age
Obesity
Mechanicals:Joint injury, joint misalignment
Genetics
Chondrodysplasias(e.g stickler syndrome)
Secondary joint damage due to inflammatory arthropathies e.g. rheumatoid arthritis

Question 23

What percent of meniscal/ACL tear victims will develop OA in the next 5-10 years

Answer 23

~50%

Question 24

Give some evidence for mechanical factors influencing the development of OA

Answer 24

Destabilising joint injuries increase risk of OA
Intra-articular fracture increases the risk of OA

Question 25

Why does lack of aggrecanase stop the loss of cartilage after joint injury?

Answer 25

Cartilage is a biologically active process, dependent on aggrecanases

Question 26

Outline the 2 pathways that lead to symptomatic OA

Answer 26

Abnormal joint + Normal load Normal joint + Abnormal load Leads to mechanical injury, leading to incorrect remodelling of cartilage Then symptomatic OA

Question 27

Do all OA cases progress?

Answer 27

No, some can remain at the same severity, or even remise

Question 28

Demographically with age and sex where is OA more prevalent?

Answer 28

With greater age and more in women

Question 29

Why are OA rates increasing?

Answer 29

Higher obesity levels, poorer diets that aren't equipped to maintain cartilage health

Question 30

How is OA diagnosed?

Answer 30

Clinically: Stiffness Pain on function Crepitus, bony deformity X-ray: Osteophytes Joint space narrowing Bone cysts Blood tests: Normal CRP Negative tests for RA Other tests to exclude secondary causes

Question 31

What are these?

Answer 31

Heberdens' nodes, diagnostic of hand OA

Question 32

Give 3 surgical options for OA treatment

Answer 32

**Total joint replacement** /‘arthroplasty’(hip or knee) is a highly effective treatment (best results when pain high, function poor, over 60, end stage radiographic disease) **Uni-compartmental replacement** for the knee is possible **Trapeziectomy** (removal of a thumb bone) is a good surgical treatment for base of thumb OA

Question 33

Outline 2 new drugs targeted at treating OA and their effects

Answer 33

SyMOADs(Symptom modifying OA drug)-Treat pain+Improve function DMOADs(Disease modifying OA drug)-Prevent/Slow early onset of OA

Question 34

What are 3 requirements for clinical trials of new OA drugs

Answer 34

-Find drugs targeting the right sites -Using the right population(Subgrouping+) -Using the right outcome measurements(Imaging+patient reported outcomes)