Musculoskeletal disease

Question 1

Which joints are the most commonly affected in osteoarthritis?

Answer 1

main load baring joints such as the hip and knee but can affect any joint
occurs in all species with loaded synovial joints

Question 2

What are the structural changes in the joints associated with oesteoarthritis? What kinds of cartilage and bone are affected?

Answer 2

• cartilage degradation
• bone formation / growths
• changes in ligaments and synovial fluids
• articular cartilage
• subcondrial boneW

Question 3

Why does oesteoarthritis cause pain?

Answer 3

• not from the cartilage as it is anerual
• damaged cartilage releases algesic signals
• bone exposure and synovial inflammation are likely the causes of pain

Question 4

What happens to the bone in oesteoarthritis and why?

Answer 4

becomes thicker and bony spurs start to protrude
like as an adaptation to help distribute the pathological load

Question 5

How is normal cartilage and bone formed in development?

Answer 5

• bone slowly replaces cartilage but a cartilage growth plate remains
• chondrocytes become proliferative and then hypertrophic and hypertrophic cells die and are replaced by bone
• after development the growth plate is lost to prioritise strength over cartilage

Question 6

How are the cartilage and bone systems subverted in osteoarthritis?

Answer 6

• cartilage cells adopt growth plate morphology
• proliferative -> hypertrophic -> die
• always trying to produce new cartilage with new bone forming beneath it

Question 7

What is the basic mechanism by which cartilage acts as a shock absorber?

Answer 7

• collagen resists swelling in response to force
• proteoglycans restore shape

Question 8

Describe the circadian rythm seen in cartilage

Answer 8

• cartilage makes its matrix proteins on a day/night cycle of making and breaking down cartilage
• disrupting this induces OA

Question 9

How can why does cartilage become lost?

Answer 9

• variety of enzymes
• collageneases cleave collagen triple helixes
• gelatinases chew it up
• aggrecanases cleave aggrecan which is produced by chondrocytes, macrophages and osteoclasts due to injurt or microdamage

Question 10

What are some risk factors of OA?

Answer 10

• age
• load (obesity)
• specific use patterns
• injury and inflammation
• genetic factors (40-60% with over 200 genes and SNPs involved)

Question 11

Give examples of two genes that are thought to increase risk of OA

Answer 11

GDF5
- seen in all joints
FRZB
- seen in some

Question 12

What other developmental factors might affect OA oether than gene SNP?

Answer 12

• epigenetics (diet induced over generations)
• joint shape is decided during development and may affect load later in life leading to OA

Question 13

What are the current treatments available for OA?

Answer 13

• drugs
• arthroplasty (hip/knee replacement)
• other surgical repairs such as osterochondrial plugs and autologous chrondrocyte implantation

Question 14

What are the negatvies of orthroplasty to treat OA?

Answer 14

• waer debris can induce chromosomal translocations in some cells
  especially metal implants
• significantly increased cobalt and chromium has been found in the blood of patients 6-24 months post op

Question 15

What is a microfracture of treat OA?

Answer 15

• removing damage to smooth the joint surface and reduce inflammation
• prevents secondary OA but only works on small defects
• make holes in the subchondrial surface to induce wound healing response
• avascular cartilage needs this help to access blood vessels below the bone

Question 16

What is a hyalograft?

Answer 16

a 3d scaffold that you can seed chondrocytes onto to try and maintain their original niche and microenvironment

Question 17

What is the difference between type 1 and hyaline cartilage?

Answer 17

hyaline reduces friction and shock while type 1 provides tensile strength and is less smooth

Question 18

What is an osterodonrial plug to treat oa?

Answer 18

• take full length of cartilage and bone from a non-weight bearing area of the joint
• create a mosaic of plugs to resurface the damaged joint
• donor site morbidity and poor integration

Question 19

What happens to chondrocytes as we age (and in OA)?

Answer 19

• decrease in number
• chondrocyte apoptosis is associated with matrix degradation and hypertrophy
• metabolism is lost and damaged cells and debris accumulate
• reduces biological signals leads to a poor cartilage repsonse to load

Question 20

what is an autologous chondrocyte implant?

Answer 20

• harvest chondrocytes from a healthy non-weight bearing joint
• cutlture to increase numbers and/or quality
• implantation into unhealthy joint using a membrane or patch