Week 3 - Synovial Joints (basics, lubrication and aging) and Hyaline Cartilage

Synovial joint purpose

Load transfer

Allow movement

How do synovial joints reduce contact stress at joints? (2)

Graduated Flexibility - Allows for contact stresses at the joint surfaces to decrease and facilitates shock absorption. Occurs through the decreasing stiffness throughout load transfer - e.g. from compact bone in shaft, to spongy bone in epiphyses, to hyaline articular cartilage, to fibrocartilage menisci

Increased Surface area - widening of bone at ends and presence of menisci increases surface area, lowering contact stresses

Implication of variable bearing area of synovial joints - what minimizes this

Whole joint surface often not in contact at once, and can reduce when in different positions. Has implications on stresses. Hyaline cartilage minimises this

Hyaline cartilage functions + fancy description of composition

Withstand and distribute applied loads in order to protect underlying bone from high contact stresses, whilst allowing relative motion of articulating surfaces with low friction and minimal surface wear

Heterogenous, anisotropic viscoelastic material

Hyaline cartilage structure + components - key things that arent components?

<10% chondrocytes, 90% ECM

ECM is 80% H2O - rest is collagen type 2 (forms mesh) and proteoglycan aggregates (7% - most concentrated in middle zone (mesh zone))

NO blood vessels, lymphatics or innervation

Collagen fibre orientation within hyaline cartilage and other important structural features (4)

Superficial zone (10-20%) where collagen is dense and woven, aligned parallel to surface - resists friction created by opposing articular surfaces

Middle zone (40-60%) where collagen is less dense and multidirectional - mesh

Deep zone (30%) collagen fibrils oriented perpendicular to base bony surface - anchored to tidemark (compression resistance)

Tide mark - border between deep zone (uncalcified cartilage) and calcified cartilage on border that connects to subchondral bone

Proteoglycan Aggregates

Large ECM molecules consisting of multiple proteoglycans linked to a single hyaluronic acid

Proteoglycan molecules in hyaline cartilage are aggrecan most commonly - protein cores with side chains of chondroitin sulfate and keratin sulfate (GAGs). These bind to hyaluronan (long filament) to form a massive macromolecule (PROTEOGLYCAN AGGREGATE) via link proteins

Their size makes them pretty much immobile - 0 diffusion and stable

Purpose of dissociation of glycosaminoglycans (GAGs) in proteoglycan aggregates

When in solution (ECM is 80% water), sulphate and carboxyl groups dissociate - negatively charged end poles create high electrostatic repulsion, which extends and stiffens the proteoglycans, taking up as much space as possible.

Donnan osmotic swelling? (Donnan effect)

Facilitates the high water content of hyaline cartilage

Immobile negative charges of the proteoglycan aggregates attracts positively charged ions of the synovial fluid (Ca2+, Na+). This then creates osmotic gradient as there is higher osmolarity within the hyaline cartilage - water enters hyaline cartilage (50% of the water can move between areas)

Donnan effect - immobile fixed charge density induces a greater osmolarity in the tissue than its surroundings)

How does PG and collagen interact within ECM?

Interwoven collagen II mesh confines PGs - reduce their domain to a 1/5 - high stiffness (collagen under tensile stress from PGs, PGs want to expand)

Spatial configuration and degree of collagen fibril interweaving determines efficiency of PG containment - how much water can move through the porous solid. When tightly woven, frictional drag resists fluid flow - inversely proportional to the permeability of the cartilage (VERY LOW)

Overall resistant to deformation through their arrangement

Mechanical behaviour of hyaline cartilage - biphasic model and rate of strain

Biphasic cartilage model - the response of cartilage to loading can be explained through 2-phase model in which its mechanical behaviour is determined by the two components of its ECM

Fluid phase - hydrostatic pressure in interstitial fluid (water) supports initial compressive load

Fluid movement (hydrostatic pressure > osmotic swelling pressure) initiates solid phase. NOTE - this will slow down in constant load application as the pores decrease in size when solid is compressed, until stopped (equilibrium between hydrostatic pressure of remaining fluid and compressive force)

Solid phase - PG aggregates and collagen interaction - their bulk compressive and shear stiffness assists in resisting compressive load

Stiffness increase with higher strain rate as solid takes bore of stress - solid phase is entered

NOTEABOUT RATE

Fluid flow in cartilage - how does this occur, and what happens after?

Compression of cartilage causes fluid to flow - initially compression resisted by hydrostatic pressure (interstitial fluid doesnt want to move due to low permeability/high frictional drag).

When hydrostatic pressure EXCEEDS osmotic swelling pressure, water begins to flow - rate of flow dependant on permeability and porosity of ECM. Flow of water through ECM pores generates frictional drag (proportional to flow rate)

As this fluid is redistributed/removed (to synovial fluid), stress transferred to solid components

permeability vs porosity of ECM

Porosity simply describes pores - space in the tissue

Permeability describes property of ease of fluid flow through material.

How to calculate frictional force after coefficient of friction is applieeeeed

Contact force x COF

Friction force dependant on: (4)

Articular surface roughness

Normal load (how much they are pressing together - creates higher normal force therefore more compressed)

Static vs kinetic conditions (static friction > kinetic)

Mode of lubrication (boundary, fluid-film or mixed)

How to quantify surface roughness, and what creates frictional resistance

Measure height of asperities from the surface midline - small peaks (nm). Hyaline cartilage is very smooth - even hip replacements not as smooth. Note asperities are so small, atomic-level forces create frictional resistance (resist shear). Movement occurs when this shear stress > shear yield point

Role of cartilage surface and synovial fluid in synovial joint lubrication? (What do they produce)

Chondrocytes in cartilage produce HA and lubricin, synoviocytes in synovial fluid produce lubricin / superficial zone protein (SZP). Both are large, hydrophilic macromolecules (extremely anionic - can absorb 1000x their own volume in water).

Notes for Boundary layer lubrication (when/components/function)

Produces HIGHEST frictional force - comes into action at high loads/low speeds (highest COF)

Articular surfaces separated by 1-2 molecules of a "sacrificial layer" - Collagen II fibres form links with lubricin and HA to create the sacrificial gel layer - gives way and replenishes 10x faster than depletion - allows for even less friction.

Notes for Fluid/film lubrication (when/components/function)

Occurs at higher speeds/lower loads - LOWEST COF

Articular surfaces separated by fluid film where distance between surfaces >3x surface roughness (asperities height). Load is supported by pressure generated in fluid - frictional resistance to fluid is very low bc it only arises from shearing of viscous fluid

Synovial fluid - function at rest

Lubricin produced in fluid facilitates HA chains to create large coil configurations - rigidity sufficient to resist external stress (external stress < yield stress). This offers some stability and resistance to flow

Synovial fluid - function during impact/instantaneous load application

HA chains formed when at rest remain coiled and linked, creating an elastic response to bear the intensive loads

Synovial fluid - function during slow loading / kinetic conditions

HA bonds broken - HA chains separate to align parallel, slipping past one another more freely. Synovial fluid can then behave like a viscous fluid

Describe the non-newtonian shear-thinning behaviour

Viscosity decreases when shear rate increases

Note it gets harder to shear the liquid - but its gets relatively easier to shear the liquid as the shear rate increases (non-linear fashion) - Rate of increase of shear stress decreases with higher shear rate

Mixed lubrication - boundary layer and fluid-film combined.

Asperities coming together and pressurised fluid present throughout the overall articulation of the surfaces - occurs throughout the body

Definition of degeneration

Structural and functional failure of the tissue

Changes due to aging vs OA of femoral hyaline cartilage - structurally

Normal aging - discolouration due to advanced glycation end products. Cartilage thickness reduces, but no structural defects

OA - cartilage lost, bone exposed, with osteophytes forming at joint margins and intercondylar area (small struts). If cartilage still present, superficial and middle zone can degenerate, with cell clusters and fibrillations extending into deep zone

Changes due to aging of femoral hyaline cartilage - cellularly

Chondrocyte density decreases - significantly in the superficial zone, which affects lubricin production. Occurs due to:

Apoptosis

Hypertrophic differentiation (process of ossification)

Decrease in proliferation

Replicative senescence (30-40x) (Can’t divide and replicate anymore - age associated)

Changes due to aging of femoral hyaline cartilage (6)- ECM (PACCET)

Loss of chondrocytes affects production of quality and sufficient quantity of ECM.

Proteoglycan turnover is over 20yrs, collagen 20->100 years - long lifespans. This exposes them to advanced glycation end products (yellowing colour visually) - affects function.

Aggrecans decrease in size, conc and composition - old aggrecan fragments occupy sites where newly synthesised aggrecan should go - leads to increased permeability and porosity and decreased H2O retention efficiency.

Collagen cross-linking - increases stiffness/brittleness

ECM calcification

Tidemarks increase and move upward - calcification moves into the deep zone, as calcified cartilage turns to bone

(note glycation - sugar molecules randomly binding to proteins/lipids - irreversible modification with age)

OA definition

Inflammatory and biomechanical whole-joint disease, characterised by progressive degeneration and loss of articular cartilage, and structural+functional changes in the entire bone.

OA risk factors (8) (GERMOFAP)

Age

Female gender

Obesity

Previous injury

Genetic inheritance

Metabolic disease e.g. diabetes

Endocrine disorders

Rheumatic diseases

Pathological changes associated with OA to HYALINE CARTILAGE (8) (CCOALSSS)

Altered lubrication - HA size+conc decreases loses viscosity and shear-thinning behaviour, lubricin synthesis decreases

Altered chondrocyte activity - cell clumping, terminally differentiated chondrocytes (the ossification process thingy), matrix degrading enzymes produced

Collagen degradation - bearing surface failure + fibrillation leads to COF increase

Aggrecan degradation/loss - loss of fixed charge density, easily deformed

Subchondral bone exposed - cysts form due to toxicity of synovial fluid to bone

Subchondral bone stiffness altered

Osteophyte formation

Synovitis - proliferation of lining cells leads to inflammation

Altered loading conditions that can affect hyaline cartilage (5?)

Excessive impact loading - dynamic stiffening (resistance to fluid flow increases with velocity of loading) - excessive leads to deformation of ECM

Prolonged static load - Fluid exudation leads to more stress on solid components - increases COF and therefore damage to cartilage

Absence of load - inadequate stimuli for chondrocytes - matrix is not maintained, can thin and break down

Change in routine distribution/rate of loading suddenly - cartilage is slow to respond and may overload. Can be a sudden change in exercise activity or post-injury

Excess shear stress (at cellular level) - causes chondrocyte hypertrophy, reduces the regular aggrecan and type II collagen expression (normally, intermittent hydrostatic pressure stimulates this), and chondrocyte apoptosis occurs as ECM homeostasis is disturbed

Why cant hyaline cartilage repair spontaneously?

Avascular, alymphatic and aneural

Low cellular density

Low metabolic activity

Inability to migrate to injury site

Changes to chondrocytes with aging (3)

Reduced synthetic capacity

Reduced concentration

Production of inflammatory mediators

Hyaline cartilage response to constant compressive load? (Creep)

Initially results in copious fluid exudation as fluid interstitial pressure is exceeded by the initial load. Afterward, fluid exudation slows down as the cartilage deforms until equilibrium reached. This is such that the internal stress = applied stress on the cartilage, as the redistributed tissue components and restored interstitial pressure now resists the load.

Hyaline cartilage behaviour in response to slow vs fast strain rate (compression)

Increasing the strain rate increases it's stiffness (viscoelastic property).

In slower rates of compression, water has time to move and redistribute, such that little frictional drag is created and tissue won't be distorted - local indentation at site of compression

Against faster compressive rates - hydrostatic pressure is raised as fluid doesnt have time to move - will try to move quickly, but met with high frictional drag - fluid cannot redistribute, so high stress on elastic components - lateral distortion of the tissue around loading site.

What determines HC permeability?

Spatial arrangement of the solid matrix of proteoglycan aggregates and collagen, which has low porosity and high resistance to fluid flow.