cartilage mechanobiology and osteoarthritis Flashcards
constitutive modelling
stress strain relationship can be described by an equation
MAXWELL BODY
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
KELVIN VOIGT BODY
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
example of a STANDARD LINEAR MODEL
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.
cartilage mechanobiology - physiochemical effects
permeability and compressive modulus
EC osmolarity - chondrocytes take pressure around them and alter activity in response to it affecting mechanical behaviour and cellular behaviour
cartilage mechanobiology - cell deformation
a) change chondrocyte volume changes activity - tough to study in vitro
constitutive modelling of articular cartilage
viscoelastic models composed of springs and dashpots –> cannot describe interstitial fluid flow
best models are biphasic and triphasic (fluid + solid+ charge)
cartilage mechanobiology - fluid transport
chondrocyte metabolism may be monitored by interstitial fluid flow in and out of the cartilage - may induce shear stress on chondrocytes
cartilage mechanobiology - hydrostatic pressure
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
cartilage mechanobiology - electrochemical transduction
matrix deformation - non uniform distribution of fixed charge densities –> electric potentials –> currents
effect of motion and loading
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
cartilage damage
swelling, joint pain (surrounding structures), stiffness, loss ROM, caused by trauma, wear and tear, infection and immobilisation.
cartilage repair issues
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
primary OA
unknown cause - usually affects the elderly
secondary OA (posttraumatic)
usually develops after a joint injury/obesity/developmental factors/meniscus or ACL tear
OA commonly affected joints
hips, knees spine - ankle have a higher proportion of posttrumatic due to susceptibility to instability
OA risk factors
genetic, age, gender, obesity, high bone density, joint injury + malalignement
diagnosing OA
- X-RAY
LOOKING FOR NARROWING OF THE JOINT SPACE, SUBCHONDRAL BONE SCLEROSIS. OSTEOPHYTE FORMATION - MRI
cartilage thickness - arthroscopy
diagnostic challenges associated with OA
- silent until pain - need early detection
- symptoms don’t match radiographic evidence
- can also effect muscles, synovial capsule and ligaments
STAGE 1 OSTEOARTHRITIS
- fibrillation of cartilage surface (DELAMINATION OF SURFACE LAYER + FORMATION OF VERTICAL FISSURES)
- decreased PG content
- increased water content
- collagen network may start to be damaged
- blood vessels cross the tidmark
- subchondral bone stiffening
STAGE 2 OSTEOARTHRITIS
- chondrocytes detect damage (osmolarity, charge density and strain changes)
- proliferate and synthesis matrix (anabolic)
- 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.
STAGE 3 OSTEOARTHRITIS
DEATH OF CHONDROCYTES
DOWN-REGULATION OF CELLS TO ANABOLIC SIGNALS
LOSS OF CARTILAGE
SUBCHONDRAL BONE THICKENING
OSTEOPHYTE FORMATION AT JOINT PERIPHERY
Conservative OA treatment
- physio
exercise
weigh loss
analgesics
anti inflammatories
surgical OA treatment
OSTEOTOMY
adding a plate and screws where a wedge has been removed - shifts load away from OA region delaying need for a replacement
direct cartilage treatment in surgery
- 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)
using animal models
can surgically induce OA by partial resection or meniscal tear or ACL resection then repeated or single impact loads.
last resorts - OA
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
