Lecture 4 - Cartilage Flashcards
Hyaline / Articular Cartilage + composition
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)
Elastic Cartilage
‘Yellow cartilage’
Found
- epiglottis, outer ear, eustachian tube
- high in elastin
Fibrocartilage
Found
- IVD, meniscus
Collagen structure and function
- triple helix - tensile strength
- crosslinks - stability
- sheets form arcs (extend from deep zone)
Function:
- immobilise PGs
- resist tension
Proteoglycans
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
Chondrocyte roles
- PG synthesis, modification, organisation
- Collagen synthesis & secretion
- matrix degradation & turnover –> controlled by cytokines, growth factors + proteases
Articular cartilage structure
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
Cartilage nutrition
Diffusion: - synovial fluid / bone - v. small molecules - slow diffusion rates Convective: - larger molecules - compressed into cartilage from synovial fluid
Cartilage function
- pre-stressed material
- spread loads (deform –> contact area increases + stress decreases)
- absorb mechanical shock
- friction lubrication
Factors affecting mechanical properties of articular cartilage (7)
- compression
- tension
- shear
- time-scale
- permeability
- pressure + charge density
- hydration
Mechanical behaviour 1 - Compression
- stiffness increases as function of GAG content
- equilibrium modulus, Ha = 0.1-2MPa
- highly loaded regions = stiffer in compression and higher PG content
Mechanical behaviour 2 - Tension
- collagen fibres take load
- E tension = 5-50MPa
- superficial zone stiffer
Mechanical behaviour 3 - Shear Loading
- 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
Mechanical behaviour 4 - Time Effects
- 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
Mechanical behaviour 5 - Permeability
- 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
Mechanical behaviour 6 - Pressure & Charge Density
Compression –> forces -ve charges closer + forces water out with dissolved +ve ions
Mechanical behaviour 7 - Hydration
Water content increases –> cartilage becomes less stiff and more permeable
Osteoarthritic cartilage has more water
Constitutive models for cartilage
Simplest: - isotropic, linearly elastic (generalised hooke's law) Viscoelastic: - springs and dashpots Most successful: - biphasic, triphasic
Biophysical factors evoked by mechanical loading of articular cartilage:
- Physiochemical effects
- chondrocytes sensitive to extracellular osmolarity - Cell deformation
- chondrocyte volume - strong influence on biosynthetic activity - Hydrostatic pressure
- modulate aggrecan biosynthesis - Fluid transport
- Chondrocyte metabolism regulated by interstitial fluid flow
- shear stress on chondrocyte –> aggrecan synthesis - Electromechanical transduction
- deformation –> FCD, electric potentials, currents
Effects of motion and loading:
- loading –> maintain healthy cartilage (increased cartilage matrix synthesis)
- immobilisation –> degeneration (loss PGs, thinning, less stiffness)
- too much loading –> degeneration
Cartilage repair problems:
- low blood supply
- lack of cells (only differentiated chondrocytes)
Osteoarthritis:
What is it?
What is the difference between primary and secondary?
What are symptoms?
- degradation of weight-bearing joints (subchondral bone & articular cartilage)
- primary: spontaneous
- secondary: post-traumatic
- £5.7bn/yr
Symptoms:
- pain
- stiffness
- loss of ROM
Osteoarthritis risk factors
- genetic
- environmental
age (>65)
female
obesity
high bone density - biomechanical (joint injury + misalignment)
Progression of OA
- Alteration of cartilage matrix
- fibrillation, delamination, tears/cracks
- less PG
- more water
- collagen II network damaged
- blood vessels cross tidemark
- subchondral bone stiffens - Chondrocyte response
- detect damage (osmolarity, charge density, strain)
- proliferate + synthesise matrix
- Matrix metalloproteases (MMPs) degrade matrix
- synthesis > degradation - Decline in chondrocyte response
- death
- loss cartilage
- subchondral bone thickening
- osteophyte formation
