Lecture 4 - Cartilage Flashcards

1
Q

Hyaline / Articular Cartilage + composition

A

Found
- joint surfaces, nose, ribs

Constituents

  • water + electrolytes (68-85% wet weight)
  • matrix: collagen II (10-20%), PG (aggrecan, 5-10%)
  • cells = chondrocytes (1-10% vol)
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2
Q

Elastic Cartilage

A

‘Yellow cartilage’
Found
- epiglottis, outer ear, eustachian tube
- high in elastin

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3
Q

Fibrocartilage

A

Found

- IVD, meniscus

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4
Q

Collagen structure and function

A
  • triple helix - tensile strength
  • crosslinks - stability
  • sheets form arcs (extend from deep zone)

Function:

  • immobilise PGs
  • resist tension
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5
Q

Proteoglycans

A

Structure:
- core protein (hyaluronan) + covalently attached sugars (GAGs) (aggrecan)

Function:

  • negatively charged - repel each other –> compressive strength
  • cartilage swells: repulsive forces + osmotic pressure

Mechanism:

  • Negative PGs - restrained by cartilage
  • counter ions into cartilage –> maintain electrostatic equilibrium
  • difference in solute conc between cartilage + synovial fluid
  • osmotic pressure draws water in –> swells
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6
Q

Chondrocyte roles

A
  • PG synthesis, modification, organisation
  • Collagen synthesis & secretion
  • matrix degradation & turnover –> controlled by cytokines, growth factors + proteases
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7
Q

Articular cartilage structure

A

Superficial:

  • high collagen density // to surface
  • low PG density
  • high chondrocyte density + elongated
  • high water content (80%)

Middle:

  • mid collagen density, unorganised
  • mid PG density
  • mid chondrocyte density + spherical
  • mid water

Deep:

  • mid density collagen |_ to surface (woven)
  • high PG
  • low chondrocyte density + spherical in columns
  • low water (65%)

Tidemark:
- calcified cartilage

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8
Q

Cartilage nutrition

A
Diffusion:
- synovial fluid / bone
- v. small molecules
- slow diffusion rates
Convective:
- larger molecules 
- compressed into cartilage from synovial fluid
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9
Q

Cartilage function

A
  • pre-stressed material
  • spread loads (deform –> contact area increases + stress decreases)
  • absorb mechanical shock
  • friction lubrication
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10
Q

Factors affecting mechanical properties of articular cartilage (7)

A
  • compression
  • tension
  • shear
  • time-scale
  • permeability
  • pressure + charge density
  • hydration
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11
Q

Mechanical behaviour 1 - Compression

A
  • stiffness increases as function of GAG content
  • equilibrium modulus, Ha = 0.1-2MPa
  • highly loaded regions = stiffer in compression and higher PG content
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12
Q

Mechanical behaviour 2 - Tension

A
  • collagen fibres take load
  • E tension = 5-50MPa
  • superficial zone stiffer
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13
Q

Mechanical behaviour 3 - Shear Loading

A
  • from joint motion
  • no volumetric change so no fluid flow
  • collagen content related
  • dynamic shear mod, G = 0.2-2.5MPa
  • rapid loading –> differences in compliance between bone and cartilage –> high shear stress at cartilage-bone boundary
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14
Q

Mechanical behaviour 4 - Time Effects

A
  • biphasic cartilage (water fluid + ECM solid)
  • rate-dependent behaviour
  • stiffen with increasing strain rate (rapid loading, no fluid flow)
  • viscoelastic (slower loading rates, fluid flow)
  • creep + stress relaxation –> flow dependent and non-flow dependent mechanisms
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15
Q

Mechanical behaviour 5 - Permeability

A
  • cartilage permeability v low
  • varies by zone (lowest in deep)
  • varies with deformation (compressed –> permeability decreases)
  • compressed –> porosity decreases & density negative charges increases –> harder to squeeze more fluid out
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16
Q

Mechanical behaviour 6 - Pressure & Charge Density

A

Compression –> forces -ve charges closer + forces water out with dissolved +ve ions

17
Q

Mechanical behaviour 7 - Hydration

A

Water content increases –> cartilage becomes less stiff and more permeable

Osteoarthritic cartilage has more water

18
Q

Constitutive models for cartilage

A
Simplest:
- isotropic, linearly elastic (generalised hooke's law)
Viscoelastic:
- springs and dashpots
Most successful:
- biphasic, triphasic
19
Q

Biophysical factors evoked by mechanical loading of articular cartilage:

A
  1. Physiochemical effects
    - chondrocytes sensitive to extracellular osmolarity
  2. Cell deformation
    - chondrocyte volume - strong influence on biosynthetic activity
  3. Hydrostatic pressure
    - modulate aggrecan biosynthesis
  4. Fluid transport
    - Chondrocyte metabolism regulated by interstitial fluid flow
    - shear stress on chondrocyte –> aggrecan synthesis
  5. Electromechanical transduction
    - deformation –> FCD, electric potentials, currents
20
Q

Effects of motion and loading:

A
  • loading –> maintain healthy cartilage (increased cartilage matrix synthesis)
  • immobilisation –> degeneration (loss PGs, thinning, less stiffness)
  • too much loading –> degeneration
21
Q

Cartilage repair problems:

A
  • low blood supply

- lack of cells (only differentiated chondrocytes)

22
Q

Osteoarthritis:

What is it?
What is the difference between primary and secondary?
What are symptoms?

A
  • degradation of weight-bearing joints (subchondral bone & articular cartilage)
  • primary: spontaneous
  • secondary: post-traumatic
  • £5.7bn/yr

Symptoms:

  • pain
  • stiffness
  • loss of ROM
23
Q

Osteoarthritis risk factors

A
  • genetic
  • environmental
    age (>65)
    female
    obesity
    high bone density
  • biomechanical (joint injury + misalignment)
24
Q

Progression of OA

A
  1. Alteration of cartilage matrix
    - fibrillation, delamination, tears/cracks
    - less PG
    - more water
    - collagen II network damaged
    - blood vessels cross tidemark
    - subchondral bone stiffens
  2. Chondrocyte response
    - detect damage (osmolarity, charge density, strain)
    - proliferate + synthesise matrix
    - Matrix metalloproteases (MMPs) degrade matrix
    - synthesis > degradation
  3. Decline in chondrocyte response
    - death
    - loss cartilage
    - subchondral bone thickening
    - osteophyte formation
25
Q

Treatment: Non-surgical and surgical

A
  • weight loss
  • exercise + stretching
  • drugs
  • supplements

Surgery

  • osteomy: wedge taken out of bone - shifts load away from OA region
  • arthroscopic washout - cleanup / debridement
  • tissue grafting / mosaicplasty
  • ACI (fibrocartilage)
  • microfracture
  • joint replacement
  • joint fusion