What are the types of cartilage and where are they found?
- Hyaline: Found in nose, ribs
- Fibrous: Found in intervertebral discs, meniscus, temporomandibular joint
- Elastic: High in elastin, found in outer ear, epiglottis
What are the main components of cartilage
- Water and electrolytes
- Matrix: Has collagen II, aggrecan, and other collagens and PGs
- Cells: Chondrocytes (1-10%)
What is structure of collagen? What is its purpose in cartilage?
- Triple helix like a biological rope providing tensile strength
- Cross linked for stability
- Arranged into sheets which form arcs
- Immobilises PGs
What is aggrecan?
The most common GAG in cartilage
Negatively charged and aggregates to hyaluronan
Draw up a table for how :
Chondrocyte density and characteristics
Collagen fibre orientation
change in the superficial middle and deep zones for cartilage
What is function of cartilage?
- Bear Loads
- Absorb mechanical shock
- Spread load
- Provide joints with excellent friction, lubrication and wear characteristics.
How does cartilage get its nutrients?
- Diffusion: Through bone and synovial fluid for very small molecules
- Convective transport: Associated with time varying loads for transport of larger solute molecules
What three mechanical tests do we use to test cartilage?
- Confined compression
- Unconfined compression
What are the factors that affect mechanical properties of cartilage?
- Time scale
- Pressure and charge density
Think about a Pr TeCh HyPe ViSh TyCo
What is role of PGs in cartilage?
Gives tissue resistance to compression
WHat are the two causes of pressure that make cartilage swell?
- Cartilage swells due to two types of pressure:
- Charge-to-charge repulsive force: Exerted by closely packed negatively charged PGs
- Donnan osmotic pressure: Due to high density of fixed negative charge in PGs
Explain how Donnan pressure works in cartilage for helping cartilage withstand loads?
- GAGs and PGs have a negative charge
- PGs are immobilised by cartilage
- Counter ions are attracted to cartilage to maintain equillibrium
- This changes the solute concentration between the cartilage and the synovial fluid
- Water is drawn into cartilage by osmotic pressure and causes cartilage to swell
How does pressure and charge density of PGs cause cartilage to swell?
- Negative charges between closely packed PGs leads to repulsive forces between the sub-units and within each sub-units
- Causes tissue to swell further
- Articular cartilage is prestressed
Label the 8 missing labels going anticlockwise from top left
- Superficial tangential zone
- Middle zone
- Deep zone
- Calcified cartilage
- Cancellous bone
- Subchondral bone
- Tide mark
- Articular surface
What affects compressive stiffness?
Compressive stiffness increases as function of total GAG content
Not corellated to collagen content
Does PG content affect tension? How does stiffness change in different parts of cartilage
- Superficial zones are stiffer than middle and deep zones.
- Collagen fibres take the load
How does permeability of cartilage change with deformation of tissue?
As cartilage is compressed its permeability decreases.
Explain how cartilage's mechanical properties depend on time scale
Cartilage is biphasic = fluid water + Solid ECM
- It has Rate dependence
- Elastic behaviour
- At rapid loading, now fluid flow
- Stiffens with increasing strain rate
What is time to equilibrium for normal cartilage?
Function of (1/thickness2)
What causes viscoelasticity and draw the graphs for creep and stress relaxation.
- Combination of flow dependent drag and non flow-dependent, intermolecular friction of collagen/proteoglycan matrix mechanisms.
What is a constitutive law?
A mathematical law that is used to experimentally determine the stress strain response
Why does cartilage have trouble recovering?
- It is avascular : No haemorrage or injury response
- No inflammatory cells to remove necrotic tissue
- It lacks cells: Lack of undifferentiated cells, only differentiated condrocytes
- Little cell migration
- Limited synthesis of matrix
what three models are there for modelling cartilage? Draw them all with their graphs too
What were the limitations of the viscoelastic models composed of springs and dashpots?
Give some more successful models.
More successful models
- Could not describe the known effects of interstitial fluid flow
- Cartilage exudes water when compressed and absorbs fluid when soaked
Biphasic: Two intrinsically incompressible and immicscible phases
- Triphasic: As above but with effects due to charge
What are the biophysical factors evoked when you load articular cartilage?
- chondrocytes sensitive to extracellular osmolarity and pressure is linked to permeability
- Cell deformation: Chondrocyte volume thought to exert strong influence on biosynthetic activity
- Tough to study in vitro though. Chondrocytes repond differently according to the zones in articular cartilage.
- Hydrostaic pressure: Thought to modulate aggrecan biosynthesis through membrane mediated pathways and through chondrocyte response
- Fluid transport: Fluid flow might regulate chondrocyte metabolism: Accelerates transport of solutes and macromolecules
- Fluid flow can induce shear stress on chondrocytes to accelerate transport of solutes and molecules
- Electromechanical transduction: Non uniform fixed charge density, electric potentials and currents due to deformation of matrix
What are the types of osteo arthiritis
Primary: Unknown cause affecting mainly elderly
- Secondary: After joint injury
- Result of obesity or developmental factors.
What are the methods of diagnosing osteoarthiritis
What are the risk factors of OA?
Describe the general pathology of OA
Primary changes: Cartilage loss, subchondral bone remodelling, osteophyte reformation
Might also affect muscles, synovial capsule and ligaments
Describe the progression of OA
- Alteration of cartilage matrix:
- Decreased proteoglycan content
- Increased water content
- Collagen II first unaffected then network may be damaged
- Blood vessels cross tidemark
- Stiffening of subchondral bone.
- Response of chondrocytes:Chondrocytes detect damage and proliferate to synthesise matrix (anabolic)
- Matrix metaloproteases degrade matrix molecules (catabolic).
- Nitric oxide released after mechanical stimulus, stimulate expression of NO through interleukin 1
- Reformation depends on balance of anabolic and catabolic
- Stage 3, death of chondrocytes:
- Loss of cartilage
- Subchondral bone thickening
- Osteophyte formation at joint periphery.
What are the treatment options for OA?
Weight loss, exercise drugs, nutrition, glucosamin sufate etc
- Altering mechanics: If OA is on one side shif the load away with a wedge.
Direct cartilage treatment (cleanup) with arthroscopic washout.
Direct cartilage tissue grafting or autologous chondrocyte cell therapy
Last resort: Joint replacement or joint distraction