Articular Cartilage Structure and Function

Water - 70-80% of Wet Weight

Distribution:

• Superficial zone: 75-80%
• Middle zone: 70-75%
• Deep zone: 65-70%
• Water content decreases with depth

Functions of water:

• Provides nutrition pathway (diffusion)
• Enables load distribution (biphasic behavior)
• Lubricates surface (hydrodynamic effect)
• Carries metabolites and waste products

Water is held in cartilage by osmotic pressure from proteoglycans and constrained by collagen network.

Collagen - 15-22% of Wet Weight

Type II collagen dominance:

• Type II collagen: 90-95% of total collagen
• Type IX collagen: 1-2% (connects Type II fibrils)
• Type XI collagen: 3% (fibril nucleation)
• Type VI, X, XII, XIV: Minor collagens

Type II collagen structure:

• Triple helix: three alpha-1(II) chains
• Fibril diameter: 20-40 nm (smaller than Type I)
• Crosslinks: hydroxylysyl pyridinoline (HP)
• Fibrils assemble into fibers

Collagen orientation by zone:

• Superficial zone: Tangential (parallel to surface)
• Middle zone: Oblique (random orientation)
• Deep zone: Perpendicular (vertical to surface)
• Calcified zone: Anchored in subchondral bone

Collagen provides tensile strength and structural framework for cartilage.

Proteoglycans - 4-7% of Wet Weight

Aggrecan is the major proteoglycan (90% of total proteoglycans):

• Molecular weight: 2-3 million Da
• Core protein: 220-250 kDa
• GAG chains: Chondroitin sulfate (CS) and keratan sulfate (KS)
• Up to 100 CS chains per molecule
• Up to 60 KS chains per molecule

Aggrecan aggregation:

• Multiple aggrecans (50-100) bind to hyaluronan backbone
• Link protein (40-45 kDa) stabilizes binding
• Aggregate molecular weight: 50-200 million Da
• One of the largest macromolecular structures in biology

Fixed negative charge density:

• Sulfate groups (SO4-) on GAG chains
• Carboxyl groups (COO-) on GAG chains
• Creates high fixed negative charge density (FCD)
• FCD highest in deep zone (250-350 mEq/L)

Other proteoglycans:

• Decorin: binds to collagen, regulates fibril assembly
• Biglycan: similar to decorin
• Fibromodulin: collagen fibril organization
• Perlecan: basement membrane around chondrocytes

Proteoglycans provide compressive stiffness through hydration and swelling pressure.

Other Matrix Components

Non-collagenous proteins (less than 1%):

• Cartilage oligomeric matrix protein (COMP)
• Fibronectin
• Tenascin
• Thrombospondin
• Matrilins

Cells (chondrocytes):

• Only 1-5% of cartilage volume
• Density: 10,000-20,000 cells/mm³
• Highest density in superficial zone
• Responsible for matrix synthesis and turnover

Chondrocyte turnover of matrix:

• Collagen half-life: greater than 100 years
• Aggrecan half-life: 3-24 years (zone dependent)
• Superficial zone: fastest turnover
• Deep zone: slowest turnover

Low cellularity and slow turnover contribute to limited healing potential.

Superficial (Tangential) Zone - 5-10% Depth

Structure:

• Collagen fibrils parallel to articular surface
• Highest collagen content (greater than 80% dry weight)
• Lowest proteoglycan content (15-20 mg/mL)
• Highest water content (75-80%)
• Small diameter collagen fibrils densely packed

Cells:

• Flattened chondrocytes parallel to surface
• Highest cell density (15,000-20,000 cells/mm³)
• Express lubricin (proteoglycan 4, PRG4)

Mechanical properties:

• Highest tensile strength
• Resists shear forces
• Provides low-friction surface

The superficial zone is the first line of defense against mechanical wear.

Middle (Transitional) Zone - 40-60% Depth

Structure:

• Collagen fibrils obliquely oriented (random, disorganized)
• Intermediate collagen content (60-70% dry weight)
• Moderate proteoglycan content (30-40 mg/mL)
• Moderate water content (70-75%)
• Larger diameter collagen fibrils than superficial zone

Cells:

• Rounded chondrocytes
• Lower cell density than superficial zone
• May be arranged singly or in pairs

Mechanical properties:

• Transitional mechanical properties
• Contributes to compressive and tensile strength

The middle zone provides a transition between superficial and deep zones.

Deep (Radial) Zone - ~30% Depth

Structure:

• Collagen fibrils perpendicular to articular surface
• Lowest collagen content (50-60% dry weight)
• Highest proteoglycan content (50-60 mg/mL)
• Lowest water content (65-70%)
• Largest diameter collagen fibrils
• Highest fixed negative charge density

Cells:

• Rounded chondrocytes arranged in columns perpendicular to surface
• Lowest cell density
• Chondrocytes may be in small groups (2-6 cells)

Mechanical properties:

• Highest compressive stiffness
• Resists compressive loads
• Lowest tensile strength

The deep zone is the primary load-bearing region under compression.

Calcified Cartilage Zone - 5-10% Depth

Structure:

• Mineralized cartilage matrix
• Type X collagen present (in addition to Type II)
• Collagen fibrils from deep zone penetrate into this zone
• Separated from deep zone by tide mark (basophilic line)

Tide mark:

• Thin basophilic line on histology
• Represents mineralization front
• Advances with aging (thicker calcified zone)
• Multiple tide marks indicate remodeling history

Function:

• Anchors articular cartilage to subchondral bone
• Provides gradual transition in mechanical properties
• Distributes loads to subchondral bone

Cells:

• Hypertrophic chondrocytes
• Lower cell density than deep zone
• Cells surrounded by mineralized matrix

The calcified zone provides a mechanical and biochemical interface between cartilage and bone.

Biphasic Theory of Cartilage Mechanics

Two phases:

1. Solid phase: Collagen-proteoglycan matrix (20-30%)
2. Fluid phase: Interstitial water (70-80%)

Behavior under load:

• Immediate response: Load carried by fluid phase (incompressible)
• Time-dependent response: Fluid exudes from matrix
• Equilibrium: Load carried by solid matrix (compressed)
• Recovery: Fluid re-imbibes when load removed

Biphasic behavior provides shock absorption and load distribution.

Mechanical Property Values

Compressive properties:

• Aggregate modulus: 0.5-0.9 MPa
• Equilibrium compressive modulus: 0.4-0.8 MPa
• Instantaneous modulus: 5-10 MPa (higher due to fluid pressurization)
• Poisson's ratio: 0.1-0.2 (drained) to 0.5 (undrained)

Tensile properties:

• Tensile modulus: 5-25 MPa (zone and direction dependent)
• Tensile strength: 5-40 MPa
• Superficial zone has highest tensile properties
• Perpendicular to surface direction is weakest

Permeability:

• Hydraulic permeability: 0.5-5 × 10⁻¹⁵ m⁴/N·s
• Decreases with increasing compression (strain-dependent)
• Lower permeability with higher proteoglycan content

Viscoelastic properties:

• Creep under constant load
• Stress relaxation under constant deformation
• Hysteresis during cyclic loading (energy dissipation)
• Frequency-dependent stiffness

Mechanical properties vary with zone, loading direction, and loading rate.

Nutrition Pathways

Two sources of nutrition:

1. Synovial fluid (superficial and middle zones)
2. Subchondral bone (deep and calcified zones)

Diffusion-based transport:

• No vascular supply in cartilage
• Nutrients diffuse through matrix
• Oxygen tension decreases from surface (10% O₂) to deep zone (1% O₂)
• Glucose is primary energy source

Load-enhanced transport:

• Cyclic loading pumps fluid in/out
• Improves nutrient transport
• Removes metabolic waste products
• Immobilization impairs nutrition

Adequate nutrition requires joint motion and cyclic loading.