cartilage mechanobiology and osteoarthritis

Question 1

constitutive modelling

Answer 1

stress strain relationship can be described by an equation

Question 2

MAXWELL BODY

Answer 2

spring in SERIES with a dashpot

if apply step change to stress see linear response in spring not creep

if apply step change to strain see stress relaxation

good for measuring stress relaxation because of dashpot bad at modelling creep because spring instantly deforms

Question 3

KELVIN VOIGT BODY

Answer 3

spring in PARALLEL with a dashpot

if apply step change in stress get creep

if apply step change to strain, get a spike, dashpot cannot react -> don’t get stress relaxation.

Good for measuring creep bad fr measuring stress relaxtion

Question 4

example of a STANDARD LINEAR MODEL

Answer 4

spring in parallel with a dashpot whole thing in series with another spring

apply a step change to stress, see individual displacement then creep caused by parallel organisation

apply step change in strain get stress relaxation.

Question 5

cartilage mechanobiology - physiochemical effects

Answer 5

permeability and compressive modulus
EC osmolarity - chondrocytes take pressure around them and alter activity in response to it affecting mechanical behaviour and cellular behaviour

Question 5

cartilage mechanobiology - cell deformation

Answer 5

a) change chondrocyte volume changes activity - tough to study in vitro

Question 5

constitutive modelling of articular cartilage

Answer 5

viscoelastic models composed of springs and dashpots –> cannot describe interstitial fluid flow

best models are biphasic and triphasic (fluid + solid+ charge)

Question 6

cartilage mechanobiology - fluid transport

Answer 6

chondrocyte metabolism may be monitored by interstitial fluid flow in and out of the cartilage - may induce shear stress on chondrocytes

Question 7

cartilage mechanobiology - hydrostatic pressure

Answer 7

a) modulate aggrecan biosynthesis
stretch activated ions open in response to mechanical stimulation, allowing calcium ions to flow into the cell, changes cell funtions. Integrin proteins extend through cell membrane and tell nucleus what is going on. G proteins extend through cytoskeleton and tell cell what is going on. Cilia informs about external environment

Question 8

cartilage mechanobiology - electrochemical transduction

Answer 8

matrix deformation - non uniform distribution of fixed charge densities –> electric potentials –> currents

Question 9

effect of motion and loading

Answer 9

loading is required to maintain healthy cartilage –> moderate exercise increased cartilage matrix synthesis, immobilization –> degeneration (loss of PGs, thinning cartilage, decreased compressive stiffness, decreased cartilage matrix synthesis.)
if overload = degeneration - change in PG content = cartilage stiffness

Question 10

cartilage damage

Answer 10

swelling, joint pain (surrounding structures), stiffness, loss ROM, caused by trauma, wear and tear, infection and immobilisation.

Question 11

cartilage repair issues

Answer 11

chondrocytes have a low cell turnover, aneural lack of communication, little cell migration, no haemorrhage (signal injury response), no inflammatory cells to remove necrotic tissue, limited synthesis of the matrix

Question 12

primary OA

Answer 12

unknown cause - usually affects the elderly

Question 13

secondary OA (posttraumatic)

Answer 13

usually develops after a joint injury/obesity/developmental factors/meniscus or ACL tear

Question 14

OA commonly affected joints

Answer 14

hips, knees spine - ankle have a higher proportion of posttrumatic due to susceptibility to instability

Question 15

OA risk factors

Answer 15

genetic, age, gender, obesity, high bone density, joint injury + malalignement

Question 16

diagnosing OA

Answer 16

1. X-RAY
   LOOKING FOR NARROWING OF THE JOINT SPACE, SUBCHONDRAL BONE SCLEROSIS. OSTEOPHYTE FORMATION
2. MRI
   cartilage thickness
3. arthroscopy

Question 17

diagnostic challenges associated with OA

Answer 17

• silent until pain - need early detection
• symptoms don’t match radiographic evidence
• can also effect muscles, synovial capsule and ligaments

Question 18

STAGE 1 OSTEOARTHRITIS

Answer 18

1. fibrillation of cartilage surface (DELAMINATION OF SURFACE LAYER + FORMATION OF VERTICAL FISSURES)
2. decreased PG content
3. increased water content
4. collagen network may start to be damaged
5. blood vessels cross the tidmark
6. subchondral bone stiffening

Question 19

STAGE 2 OSTEOARTHRITIS

Answer 19

1. chondrocytes detect damage (osmolarity, charge density and strain changes)
2. proliferate and synthesis matrix (anabolic)
3. MMPs degrade matrix molecules (catabolic) - NO released after mechanic stimulus, NO induces interleukin- I which stimulates expression of MMPs

IF anabolic > catabolic - repair response may stabilise or restore tissue.

Question 20

STAGE 3 OSTEOARTHRITIS

Answer 20

DEATH OF CHONDROCYTES
DOWN-REGULATION OF CELLS TO ANABOLIC SIGNALS
LOSS OF CARTILAGE
SUBCHONDRAL BONE THICKENING
OSTEOPHYTE FORMATION AT JOINT PERIPHERY

Question 21

Conservative OA treatment

Answer 21

• physio
  exercise
  weigh loss
  analgesics
  anti inflammatories

Question 22

surgical OA treatment

Answer 22

OSTEOTOMY
adding a plate and screws where a wedge has been removed - shifts load away from OA region delaying need for a replacement

Question 23

direct cartilage treatment in surgery

Answer 23

• arthroscopic washout and debridement (only for stage 1)
• tissue grafting
• osteochondral allograft/autograft
• autologous chondrocyte therapy produces firo cartiflage
• microfracture - limited success in producing cartilage (produces fibrocartilage)

Question 24

using animal models

Answer 24

can surgically induce OA by partial resection or meniscal tear or ACL resection then repeated or single impact loads.

Question 25

last resorts - OA

Answer 25

joint replacement
arthrodesis (joint fusion)
joint distraction ( very rare) - distracted knee joint decreases loading on cartilage surfaces to let it recover over time - just pulling bone surfaces apart