Articular Cartilage Structure and Function

What it is. Articular cartilage is a specialised connective tissue covering the ends of bones in synovial joints. It provides a smooth, low-friction surface for joint motion and distributes load to the underlying subchondral bone.

Why its structure matters. The tissue is avascular, aneural and alymphatic, which is why cartilage injuries have limited healing potential and why its nutrition has to arrive by diffusion. Osteoarthritis is the same structure failing: loss of proteoglycans, disruption of the collagen network and changes in water content all contribute to cartilage degeneration, so the normal tissue has to be understood before the diseased one can be.

How to think about it. Mechanically, cartilage is a composite in which a collagen network constrains the swelling pressure of the proteoglycans, and a biphasic material in which a mobile fluid phase and a solid matrix interact under load. Four zones, differing in collagen orientation and composition, give the tissue different properties at the surface and at the bone. Each of these ideas has its own section below.

Water, collagen and proteoglycans make up 95-98% of cartilage. Each has a mechanical job: water is the fluid phase that carries load and nutrients, collagen resists tension, and proteoglycans resist compression, with the collagen network constraining the proteoglycan swelling to form the composite.

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WaterCollagenProteoglycansCells and Other Components

Water is 70-80% of wet weight, and it is not evenly distributed: 75-80% in the superficial zone, 70-75% in the middle zone and 65-70% in the deep zone, falling with depth. It is held in the tissue by the osmotic pressure of the proteoglycans and constrained by the collagen network.

What the water does. It is the diffusion pathway for nutrition, it carries metabolites and waste products, and its hydrodynamic effect lubricates the surface. Under load it is the fluid phase of the biphasic material, moving through the porous matrix to distribute the load; the time course of that flow is set out under Mechanical Properties.

Collagen is 15-22% of wet weight, and Type II makes up 90-95% of it. The minor collagens have specific roles:

• Type IX (1-2%) connects Type II fibrils
• Type XI (3%) nucleates fibrils
• Types VI, X, XII and XIV are minor collagens

The Type II fibril. A triple helix of three alpha-1(II) chains, assembled into fibrils 20-40 nm in diameter, smaller than Type I, and crosslinked by hydroxylysyl pyridinoline (HP). The fibrils assemble into fibres, and the fibres provide the tensile strength and the structural framework of the tissue.

The arcade. The fibres form an arcade: anchored in subchondral bone, they rise perpendicular to the surface through the deep zone, arch through the middle zone and run tangential to the surface in the superficial zone. This architecture resists the tensile stresses of joint loading and provides the framework that constrains proteoglycan swelling.

Proteoglycans are 4-7% of wet weight, and aggrecan is 90% of them. Each aggrecan molecule weighs 2-3 million Da: a core protein of 220-250 kDa carrying up to 100 chondroitin sulfate chains and up to 60 keratan sulfate chains.

Aggregation. Between 50 and 100 aggrecans bind along a hyaluronan backbone, each attachment stabilised by a link protein (40-45 kDa). The aggregate weighs 50-200 million Da, one of the largest macromolecular structures in biology.

Fixed charge. The sulfate (SO4-) and carboxyl (COO-) groups on the GAG chains give the matrix a high fixed negative charge density (FCD), highest in the deep zone at 250-350 mEq/L.

Chondroitin sulfate (CS)

Location

Distributed along core protein

Negative Charge

High (SO4-)

Function

Main water-attracting GAG

Keratan sulfate (KS)

Location

N-terminal region of core

Negative Charge

Moderate (SO4-)

Function

Increases with age

Hyaluronan (HA)

Location

Backbone for aggregation

Negative Charge

Low (COO- only)

Function

Organises aggrecan aggregates

GAG Chain Characteristics

GAG Type	Location	Negative Charge	Function
Chondroitin sulfate (CS)	Distributed along core protein	High (SO4-)	Main water-attracting GAG
Keratan sulfate (KS)	N-terminal region of core	Moderate (SO4-)	Increases with age
Hyaluronan (HA)	Backbone for aggregation	Low (COO- only)	Organises aggrecan aggregates

Proteoglycan Swelling Pressure

The negative charges on the GAG side chains attract cations (Na+, Ca2+) and water by Donnan osmotic pressure, creating a swelling pressure of 0.1-0.3 MPa that gives the tissue its compressive stiffness. The collagen network constrains that swelling, so the matrix is under prestress even without an external load.

Other proteoglycans. Decorin binds collagen and regulates fibril assembly; biglycan is similar to decorin; fibromodulin organises collagen fibrils; perlecan forms the basement membrane around chondrocytes.

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Non-collagenous proteins are less than 1% of the tissue: cartilage oligomeric matrix protein (COMP), fibronectin, tenascin, thrombospondin and the matrilins.

Chondrocytes occupy only 1-5% of cartilage volume, at 10,000-20,000 cells/mm³, most densely in the superficial zone. They are responsible for matrix synthesis and turnover.

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Turnover is slow. Collagen has a half-life of over 100 years, so it is essentially permanent; aggrecan turns over in 3-24 years depending on zone, fastest in the superficial zone and slowest in the deep. Chondrocytes in adult cartilage have low metabolic activity, and proteoglycan turnover, though faster than collagen, is still slow compared with other tissues. Low cellularity and slow turnover both contribute to the limited healing potential of the tissue.

Cartilage is built in four zones that differ in collagen orientation, composition and mechanical role, from a surface that has to slide to a base that has to hold on to bone.

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Superficial ZoneMiddle ZoneDeep ZoneCalcified Cartilage

Structure. The tangential zone, the outer 5-10%, has the most collagen as small-diameter fibrils densely packed parallel to the surface, the least proteoglycan and the most water. Its chondrocytes are flattened, lie parallel to the surface and are the densest in the tissue at 15,000-20,000 cells/mm³.

Function. The zone has the highest tensile strength in the tissue, resists shear and provides the low-friction surface: it is the first line of defence against mechanical wear.

Lubricin

Superficial zone chondrocytes uniquely express lubricin (proteoglycan 4, PRG4, superficial zone protein), secreted onto the articular surface and into the synovial fluid to provide boundary lubrication. Loss of lubricin increases cartilage wear.

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Structure. The transitional zone occupies 40-60% of the depth. Its collagen fibrils are larger in diameter than those of the superficial zone and run obliquely, in a random, disorganised arrangement, with moderate proteoglycan and water. The chondrocytes are rounded, less dense than in the superficial zone, and lie singly or in pairs.

Function. Its mechanical properties are transitional between surface and depth, contributing to both compressive and tensile strength.

Structure. The radial zone is about 30% of the depth. Its collagen fibrils are the largest in diameter and run perpendicular to the surface, but collagen is at its lowest and proteoglycan at its highest, giving the highest fixed negative charge density in the tissue. The chondrocytes are rounded, at the lowest density of the uncalcified zones, and arranged in columns perpendicular to the surface in small groups of 2-6 cells.

Function. The highest proteoglycan content gives the greatest swelling pressure and the highest compressive stiffness, so this is the primary load-bearing region under compression. The perpendicular collagen anchors the matrix to the calcified cartilage and resists the vertical compressive forces transmitted to subchondral bone. Its tensile strength is the lowest of the zones.

Structure. The calcified zone, 5-10% of the depth, is mineralised cartilage matrix containing Type X collagen in addition to Type II. Its cells are hypertrophic chondrocytes surrounded by mineralised matrix, at a lower density than in the deep zone.

Function. It is the mechanical and biochemical interface between cartilage and bone: it anchors the articular cartilage to subchondral bone, provides a gradual transition in mechanical properties and distributes load to the bone. It is separated from the deep zone by the tide mark and from bone by the cement line; the two boundaries are described below.

Two Boundaries, Not One

The tide mark is the boundary examiners ask about first, but it is the second boundary that explains how the tissue fails. The two are not interchangeable.

The tide mark separates the uncalcified deep (radial) zone from the calcified zone. It is a thin basophilic line on histology and it is the mineralisation front, not a mechanical join. The literature writes it as one word, tidemark, and both forms appear in textbooks.

The cement line separates the calcified cartilage from the subchondral bone plate beneath it. This is the true osteochondral junction.

The crossing rule. Collagen fibrils from the radial zone pass through the tide mark and anchor into the calcified layer, which is why the uncalcified cartilage is firmly continuous with the calcified layer. Those fibrils do not cross the cement line: the calcified cartilage is joined to bone by interdigitation of the two mineralised surfaces rather than by a continuous fibrillar network.

Two consequences follow, and both are worth being able to state:

• The cement line is the mechanical weak point in shear, which is why osteochondral fragments and flaps characteristically separate at or just above the subchondral plate rather than peeling off within the cartilage itself
• The interface is a gradient, not a step. Stiffness rises steeply from uncalcified cartilage through calcified cartilage to subchondral bone, and the calcified layer exists precisely to spread that mismatch over a few hundred micrometres. Anything that stiffens the subchondral plate, sclerosis or the bone reaction after marrow stimulation, steepens the gradient and concentrates shear at the junction

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Articular cartilage owes its mechanical properties to its biphasic composition and its zonal organisation.

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Biphasic BehaviourProperty ValuesNutrition and Metabolism

Two phases. The solid phase is the collagen-proteoglycan matrix, 20-30% of the tissue; the fluid phase is the interstitial water, 70-80%. Under load the incompressible fluid carries the load first, then exudes through the matrix, and only at equilibrium is the load carried by the compressed solid. Unloading reverses the sequence as fluid is re-imbibed. This is what gives the joint its shock absorption and load distribution.

Cartilage Response to Load

Load AppliedTime 0

Instantaneous deformation of 1-2%. The load is supported by the fluid phase and there is no fluid flow yet, so the cartilage behaves as an incompressible material.

Fluid FlowSeconds to Minutes

Water flows from the compressed region through the porous matrix. Deformation progresses (creep) as the load is gradually transferred to the solid matrix and the interstitial fluid pressure falls.

EquilibriumHours

Fluid flow ceases at an equilibrium deformation of 10-20%. The load is fully supported by the compressed and stressed solid matrix of collagen and proteoglycans.

RecoveryAfter Unloading

Osmotic pressure from the proteoglycans draws fluid back into the matrix and the cartilage swells to its original thickness. Recovery takes hours to days depending on the duration of loading.

Cartilage in Daily Life

Normal daily activities compress cartilage by 10-20%, which recovers overnight during sleep.

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

Aggregate modulus

Value

0.5-0.9 MPa

Note

Compressive

Equilibrium compressive modulus

Value

0.4-0.8 MPa

Note

Compressive

Instantaneous modulus

Value

5-10 MPa

Note

Higher because of fluid pressurisation

Poisson's ratio

Value

0.1-0.2 (drained) to 0.5 (undrained)

Note

Compressive

Tensile modulus

Value

5-25 MPa

Note

Zone and direction dependent; highest in the superficial zone, weakest perpendicular to the surface

Tensile strength

Value

5-40 MPa

Note

Tensile

Hydraulic permeability

Value

0.5-5 × 10⁻¹⁵ m⁴/N·s

Note

Decreases with increasing compression (strain-dependent) and with higher proteoglycan content

Mechanical Properties of Articular Cartilage

Property	Value	Note
Aggregate modulus	0.5-0.9 MPa	Compressive
Equilibrium compressive modulus	0.4-0.8 MPa	Compressive
Instantaneous modulus	5-10 MPa	Higher because of fluid pressurisation
Poisson's ratio	0.1-0.2 (drained) to 0.5 (undrained)	Compressive
Tensile modulus	5-25 MPa	Zone and direction dependent; highest in the superficial zone, weakest perpendicular to the surface
Tensile strength	5-40 MPa	Tensile
Hydraulic permeability	0.5-5 × 10⁻¹⁵ m⁴/N·s	Decreases with increasing compression (strain-dependent) and with higher proteoglycan content

Viscoelasticity. The response is time-dependent: the tissue creeps under a constant load, relaxes under a constant deformation, dissipates energy as hysteresis during cyclic loading, and its stiffness depends on loading frequency.

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Two sources. With no vascular supply, nutrients reach the chondrocytes by diffusion through the matrix from two directions: synovial fluid supplies the superficial and middle zones and subchondral bone the deep and calcified zones. Oxygen tension falls from 10% at the surface to 1% in the deep zone, and glucose is the primary energy source.

Loading as a pump. Cyclic loading pumps fluid in and out of the tissue, improving nutrient transport from synovial fluid to the chondrocytes and removing metabolic waste products. Immobilisation impairs the pump and with it the nutrition of the tissue: adequate nutrition requires joint motion and cyclic loading.

Chondrocyte Metabolism

Chondrocytes are adapted to a low-oxygen environment (1-10% O₂ compared with 21% in air) and rely primarily on anaerobic glycolysis for ATP. This low metabolic rate contributes to slow matrix turnover and limited healing capacity.

Structure explains three clinical problems, each developed in its own right elsewhere: why the tissue cannot regenerate itself once damaged (cartilage healing and repair), how chondral defects are graded and treated (articular cartilage injuries), and how the zonal architecture is read on MRI (MRI cartilage assessment).

Osteoarthritis

Early change. Proteoglycan depletion is one of the earliest changes in osteoarthritis. Loss of aggrecan reduces the fixed negative charge and with it the compressive stiffness; paradoxically the water content rises early, as the constraining collagen network fails, and the matrix softens. Surface fibrillation follows as the protective superficial zone fails.

Progression. Collagen network disruption follows proteoglycan loss, and once the collagen arcade is damaged the cartilage cannot maintain its integrity. Full-thickness defects expose subchondral bone and the joint articulates bone on bone.

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The enzymatic cascade. Cartilage breakdown is an active, enzyme-mediated process in which chondrocytes, driven by inflammatory cytokines and mechanical overload, shift from matrix maintenance to net catabolism. A basic-science viva commonly moves from what is lost to how it is degraded.

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Grading the Chondral Lesion

Before any repair decision the lesion is graded. Two systems dominate: the classic Outerbridge classification, originally for chondromalacia patellae and now applied generally, and the ICRS (International Cartilage Regeneration & Joint Preservation Society) arthroscopic grade, which the ICRS algorithm uses to drive repair choice. Both run from intact surface to full-thickness loss exposing bone.

Why grading drives management. Grade and defect size together select the technique. Low-grade (Outerbridge/ICRS I-II) lesions are usually managed non-operatively or with debridement; symptomatic full-thickness (grade III-IV) focal defects are the ones considered for marrow stimulation, ACI/MACI or osteochondral grafting. The examinable threshold is depth past the subchondral plate: marrow stimulation relies on breaching the plate, which only a grade IV lesion, or a grade III lesion converted at surgery, provides. ICRS grade, lesion size, depth and location are exactly the variables the ICRS treatment algorithm uses.

Repair

Healing capacity. Partial-thickness defects do not heal spontaneously, because the tissue is avascular. Full-thickness defects that extend to subchondral bone may heal with fibrocartilage (Type I collagen) laid down by marrow-derived mesenchymal stem cells.

The treatments in use are each built on that biology:

• Microfracture and drilling penetrate subchondral bone to recruit MSCs for fibrocartilage repair
• ACI and MACI implant cultured chondrocytes to regenerate hyaline-like cartilage
• Osteochondral grafts transplant intact hyaline cartilage from non-weight-bearing areas

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The three cartilages. A common viva trap is to confuse hyaline articular cartilage with fibrocartilage and elastic cartilage; they are distinguished by collagen type, location and mechanical behaviour.

Controversies and Areas of Uncertainty

Best repair technique. There is no consensus single best technique for focal chondral defects. Microfracture is cheaper and single-stage but yields fibrocartilage with deterioration after 2 to 5 years; ACI/MACI and osteochondral techniques may give more durable hyaline-like tissue but are costlier and may be two-stage. Defect size, location, depth and patient age all modify the choice.

Tide mark and subchondral bone. The role of the subchondral bone plate and calcified zone in osteoarthritis, initiation or consequence, is debated. Whether tide-mark advancement and subchondral change drive cartilage loss, or merely follow it, remains an active research question that influences whether therapies should target bone, cartilage or both.

Regeneration versus repair. True regeneration of zonally organised hyaline cartilage with a restored collagen arcade has not been reliably achieved in humans; current techniques produce repair tissue of variable quality. Whether scaffolds, growth factors, or gene and cell therapy can recreate the depth-dependent architecture is unresolved.

Lubrication. The relative contribution of boundary lubrication (lubricin, hyaluronan), fluid-film and interstitial-fluid-pressurisation mechanisms to the very low friction of cartilage is still actively studied, with implications for viscosupplementation and lubricin-based therapies.

Articular cartilage structure underpins the global burden of osteoarthritis and the choice of cartilage-repair strategies. Recommendations vary by society and by resource setting.