Cartilage Histology

the musculoskeletal system comprises ___, ___, and ___

cartilage, bone, and skeletal muscle

cartilage and bone are ___ tissues

cartilage and bone are specialized connective tissues

cartilage is vascular/avascular?

avascular

primary functional component of cartilage tissue?

ECM (constitutes over 95% of cartilage volume)

what are chondrocytes?

• Chondrocytes are mature cartilage cells derived from chondroblasts that are embedded in the extracellular matrix (lacunae), where they produce and maintain this matrix but can no longer divide.

• ECM products include:

  • type II collagen (in all cartilages)

  • elastic fibres (only in elastic cartilage)

  • proteoglycans

    • contribute to compressive resistance and water retention

    • e.g.: aggrecan

  • glycoproteins

    • mediate. adhesion between chondrocytes and ECM components

    • e.g.: chondronectin

how does nutrient and waste exchange occur in cartilage?

Nutrient and waste exchange in cartilage occurs by passive diffusion through the hydrated extracellular matrix, sourced from perichondrial capillaries or synovial fluid, and aided by mechanical compression—a necessity due to the tissue’s avascular nature.

what is the perichondrium?

The perichondrium is a layer of connective tissue that surrounds elastic and extra-articular hyaline cartilage but not fibrocartilage nor articular hyaline cartilage. It is composed of:

• Outer fibrous layer:

  • Composition: Dense irregular connective tissue (rich in type I collagen fibres), blood vessels, lymphatics, and nerves

  • Function: Provides mechanical protection and nourishment to the cartilage via diffusion

• Inner chondrogenic (cellular) layer: contains progenitor cells that can regenerate cartilage.

  • Composition: Contains chondroprogenitor (mesenchymal) cells

  • Function: Responsible for appositional growth of cartilage by differentiating into chondroblasts, which produce new extracellular matrix

what types of cartilage are there?

• hyaline cartilage

  • articular

  • extra-articular

    • related to structural support

    • related to bone growth

• elastic cartilage

• fibrocartilage

what is hyaline cartilage? what does it contain? where is it found? what are its functions?

• what is hyaline cartilage?

  • it is the most abundant type of cartilage in the body

  • forms embryonic skeleton, which is later replaced by bone through endochondral ossification

• what does it contain?

  • matrix containing primarily type II collagen fibres, along with GAGs, proteoglycans, and multi-adhesive glycoproteins

• where is it found?

  • articular surfaces of synovial joints (articular cartilage)

  • nose, trachea, bronchi, costal cartilages

  • epiphyseal growth plates, temporary fetal skeleton

• what are its functions?

  • provides a low-friction surface in synovial joints and distributes applied forces to underlying bone

what is elastic cartilage

• distinguished but the presence of elastic fibres and elastic lamellae within its matrix, in addition to components found in hyaline cartilage

  • chondrocytes, ECM (Type II collagen fibres, proteoglycans, glycoproteins)

• forms a dense network of branching of anastomosing fibres and interconnecting sheets of elastic material

• provides flexibility and support

• found in external ear, walls of the external acoustic meatus, auditory (Eustachian) tube, and epiglottis of larynx

  • mnemonic: four Es

what is fibrocartilage

• a strong, dense type of cartilage specialized for resistance to tensile forces. It is hard and nonelastic, making it the strongest type of cartilage.

• characterized by a matrix containing abundant type I collagen fibres, as well as the matrix components of hyaline cartilage (chondrocytes, ECM {Type II collagen fibres, proteoglycans, glycoproteins})

  • no perichondrium

• it is considered a combination of denser regular connective tissue and hyaline cartilage

• locations: intervertebral discs, menisci of the knee joint, pubic symphysis

• function: provides strong resistance to tensile and compressive forces, enabling shock absorption and structural support in load-bearing joints.

___ is the most abundant type of cartilage, while ___ is the strongest

hyaline cartilage is the most abundant type of cartilage, while fibrocartilage is the strongest

components of hyaline cartilage

• type II collagen fibres (alongside smaller amounts of other types of collagen)

• proteoglycans (e.g.: aggrecan)

  • GAGs + core protein

• proteoglycan aggregates

  • proteoglycans + hyaluronic acid

• multi-adhesive glycoproteins (including fibronectin)

what is the function of hyaline cartilage

to provide a low-friction surface in synovial joints and to distribute applied forces to underlying bone

hyaline cartilage forms the ___, which is later replaced by bone through ___ ossification

hyaline cartilage forms the embryonic skeleton, which is later replaced by bone through endochondral ossification

where is hyaline cartilage found in the body?

• articular hyaline cartilage

  • articular surfaces of synovial joints

    • knee (tibiofemoral joint)

    • hip (femoroacetabular joint)

    • shoulder (glenohumeral joint)

• extra-articular hyaline cartilage

  • structural support

    • nasal cartilage (nasal septum)

    • laryngeal cartilage (thyroid and cricoid cartilage)

    • costal cartilage

  • developmental cartilage

    • epiphyseal growth plates in growing bones

    • temporary embryonal/fetal skeleton pior to ossification

elastic cartilage is characterized by the presence of ___, and ___ in addiction to the typical components of hyaline cartilage (chondrocytes, type II collagen, proteoglycans, glycoproteins)

• elastic fibres

• elastic lamellae

What gives elastic cartilage its high resilience and flexibility?

• Elastic cartilage contains an ECM with a threadlike meshwork of elastic fibers.

• These fibers branch and anastomose, forming a dense, interconnected network that allows the tissue to bend and recoil without damage.

function and location of elastic cartilage

provides flexibility and support and is found in locations requiring such properties, including the external ear, walls of the external acoustic meatus, auditory (Eustachain) tube, and epiglottis of the larynx.

which types of cartilage are and aren't surrounded by a perichondrium?

• perichondrium present

  • extra-articular hyaline cartilage

  • elastic cartilage

• no perichondrium present

  • articular hyaline cartilage

  • fibrocartilage

unlike hyaline cartilage, the matrix of elastic cartilage does not ___ with aging, and elastic fibres can be highlighted using ___ staining

unlike hyaline cartilage, the matrix of elastic cartilage does not calcify with aging, and elastic fibres can be highlighted using orcein staining

fibrocartilage is considered a mixture of ___ and ____

fibrocartilage is considered a mixture of dense regular connective tissue and hyaline cartilage

contents of fibrocartilage

• Fibroblasts: within extracellular matrix

• Chondrocytes: Present in small numbers, embedded in lacunae.

• Extracellular matrix (ECM):

  • Dense type I and type II collagen fibers: Provide high tensile strength and resistance to pressure.

  • Proteoglycans: Attract water and contribute to resistance against compression.

  • Glycoproteins: Such as chondronectin, which helps bind chondrocytes to the ECM.

fibrocartilage:

in histological sections, chondrocytes appear as ___, while fibroblasts show ___.

• rounded nuclei with a small amount of surrounding amorphous matrix, embedded in lacunae

• flattened or elongated nuclei within fibrous areas

function and location of fibrocartilage

• provides tensile strength and resistance to compression

• intervertebral discs, menisci of the knee, and the pubis symphysis

fibrocartilage does not have a ___, and relies on ___ from surrounding tissues for nutrient and waste exchange. therefore, it has a low ___

• perichondrium

• diffusion

• regenerative capacity

which type of cartilage is the strongest?

fibrocartilage

describe glycosaminoglycans (GAGs)

• fundamental component of the ECM in connective tissues

• unbranched polysaccharide chains

• highly negatively charged → attracting water and forming a hydrated gel → ability to resist compression

• bound to a protein core to form proteoglycans (such as aggrecan)

• proteoglycan aggregates are formed from multiple aggregate molecules binding to hyaluronic acid (a GAG that does not attach to a core protein)

ground substance is composed of

• Proteoglycans: Large molecules with glycosaminoglycan (GAG) side chains (e.g., aggrecan) that attract and retain water, contributing to cartilage’s resistance to compression.

• Glycoproteins: Such as chondronectin, which facilitate adhesion between chondrocytes and the ECM.

• Water: The ECM is highly hydrated, which supports diffusion and mechanical resilience.

what are proteoglycans

Proteoglycans are large molecules in the cartilage extracellular matrix composed of:

• A core protein

• Multiple glycosaminoglycan (GAG) side chains (e.g., chondroitin sulfate, keratan sulfate)

These structures:

• Attract water due to their negative charge

• Form aggregates (e.g., aggrecan with hyaluronic acid)

• Provide compressive strength and resilience to cartilage

They are essential for maintaining the hydrated, gel-like consistency of cartilage ground substance.

what are glycosaminoglycans (GAGs)

Glycosaminoglycans (GAGs) are long, unbranched polysaccharide chains composed of repeating disaccharide units. They are:

• Highly negatively charged, attracting water and cations

• Hydrophilic, contributing to the gel-like, compressive-resistant nature of cartilage

• Commonly found as side chains on proteoglycans (e.g., in aggrecan)

Examples include chondroitin sulfate, keratan sulfate, and hyaluronic acid.

relate ground substance, proteoglycan aggregates, GAGs, and proteoglycans to each other

contrast the different fibres found in different types of cartilage

• Type II collagen

  • found in all cartilage types (highest amount found in hyaline cartilage)

  • provides tensile strength

  • produced by chondrocytes

• Type I collagen

  • found mainly in fibrocartilage

  • adds additional strength

  • produced by fibroblasts

• Elastic fibers

  • found only in elastic cartilage

  • provide flexibility and elasticity

  • produced by chondrocytes

what are multi-adhesive glycoproteins?

components of cartilage extracellular matrix that:

• Link chondrocytes to the ECM by binding collagen fibers, proteoglycans, and cell surface receptors

• Help organize ECM structure and mediate cell adhesion, migration, and signaling

• Example: Chondronectin, which connects type II collagen and proteoglycans to chondrocytes

They are essential for maintaining the structural integrity and functional interactions within cartilage.

what are the three regions of hyaline cartilage matrix based on staining properties?

• capsular (pericellular) matrix

• territorial matrix

• interterritorial matrix

capsular (pericellular) matrix

• Thin ring surrounding each chondrocyte

• Richest in glycosaminoglycans (GAGs) and type VI collagen

• Stains darkest (most basophilic) due to high GAG content

• Acts as a protective microenvironment, regulating nutrient exchange and mechanical stress

territorial matrix

• Immediately surrounds isogenous groups (clusters of chondrocytes from the same progenitor)

• Intermediate staining intensity

• Contains more GAGs than the interterritorial matrix but less than the capsular matrix

• Contains a moderate amount of collagen fibres (less than the capsular matrix)

interterritorial matrix

• Located between isogenous groups (forms bulk of cartilage tissue)

• Lightest staining region

• Rich in type II collagen, with lower GAG content

• Provides tensile strength and resistance to compression

what are lacunae?

Lacunae are small cavities within the cartilage extracellular matrix where mature cartilage cells, known as chondrocytes, reside.

• Chondrocytes become embedded in lacunae as they mature from chondroblasts.

• The lacunae provide a protected space for chondrocytes to maintain and regulate the surrounding matrix.

• These structures are especially visible in histological sections of cartilage.

what are isogenous groups?

Isogenous groups (also called isogenic groups) are clusters of chondrocytes that originate from a single chondroblast through cell division. These daughter cells:

• Are genetically identical

• Remain close together within a shared territorial matrix

• Are housed in individual lacunae but appear grouped due to limited matrix separation

Isogenous groups are a hallmark of interstitial growth in cartilage, especially during development and in the epiphyseal growth plates.

what are fibroblasts?

Fibroblasts are the most common resident cells in connective tissue. They originate from mesenchymal stem cells and play a critical role in maintaining the extracellular matrix (ECM).

Key features:

• Function: Synthesize and organize ECM components such as collagen and elastin

• Morphology: Spindle-shaped, branching cells with abundant rough endoplasmic reticulum and a prominent Golgi apparatus

• State: When metabolically less active, they are called fibrocytes

Fibroblasts are essential for tissue maintenance, repair, and wound healing.

contrast articular and extra-articular cartilage in terms of location, function, and presence of a perichondrium

Articular Hyaline Cartilage

• Location: Covers bone surfaces in synovial joints (e.g., femoral condyles, humeral head)

• Function:

  • Reduces friction

  • Absorbs mechanical shock

  • Enables smooth joint movement

• Perichondrium: Absent

Extra-articular Hyaline Cartilage

• Location: Found outside joints (e.g., tracheal rings, nasal septum, costal cartilages)

• Function:

  • Provides structural support

  • Maintains shape with some flexibility

• Perichondrium: Present

what are the zones of articular cartilage?

1. superficial (tangential) zone

2. middle (transitional) zone

3. deep (radial) zone

4. calcified zone

describe the superficial (tangential) zone of articular cartilage

• Closest to joint surface

• Flattened chondrocytes

• Collagen fibers aligned parallel to the surface

• Provides a smooth, gliding surface and resists shear forces

• Why “tangential”?

  • The collagen fibers here run parallel (tangential) to the articular surface.

  • This arrangement helps resist shear forces during joint movement.

describe the middle (transitional) zone of articular cartilage

• Rounder chondrocytes

• Random orientation of collagen fibers

• in between superficial (tangential) and deep (radial) zone

• Serves as a transitional layer; absorbs compressive forces

describe the deep (radial) zone of articular cartilage

• Chondrocytes arranged in columns

• Collagen fibers perpendicular to the surface

• Provides the greatest resistance to compressive loads

• Why “radial”?

  • The collagen fibers are oriented perpendicularly (radially) to the articular surface.

  • This orientation resists compressive forces transmitted through the joint.

describe the calcified zone of articular cartilage

• Anchors cartilage to subchondral bone

• Contains mineralized matrix and hypertrophic chondrocytes

• Separated from deep zone by the tidemark (a histological boundary)

what are the two types of cartilage growth?

• appositional growth

• interstitial growth

what is appositional growth

• Growth at the surface of existing cartilage

• Involves chondroblasts derived from progenitor cells in the inner perichondrium

• Chondroblasts secrete extracellular matrix and mature into chondrocytes

• Results in increased cartilage width (thickness)

• Requires a perichondrium → does not occur in articular cartilage or fibrocartilage

• Important in cartilage repair and postnatal growth.

what is interstitial growth?

• Growth from within the cartilage (independent of the perichondrium)

• Involves chondrocytes dividing in their lacunae

• Daughter cells form isogenous groups

• Expands cartilage internally and increases length and volume of cartilage

• Important in early cartilage development and in cartilage lacking perichondrium (e.g., articular cartilage, fibrocartilage)

explain the repair of hyaline cartilage

• Very limited repair capacity, even after minor injuries

• Impaired healing due to:

  • Avascularity

  • Immobile chondrocytes

  • Low proliferative ability of mature chondrocytes

• Repair only occurs if the perichondrium is involved:

  • Progenitor cells from the inner perichondrium may respond

  • Results mostly in dense connective tissue, not new cartilage

• Articular cartilage, which lacks perichondrium, shows no true regeneration

• Molecular repair is minimal and uncoordinated:

  • Dominated by scar tissue (type I collagen)

  • Limited restoration of normal type II collagen matrix

• Chronic damage leads to cartilage loss, joint space narrowing, and formation of bone spurs (osteophytes)

explain the calcification of hyaline cartilage

• Hyaline cartilage can undergo calcification, particularly as part of aging or during endochondral ossification.

• This process involves mineralization of the extracellular matrix.

• Chondrocytes hypertrophy, secrete enzymes (e.g., matrix metalloproteinases), and initiate deposition of calcium salts.

• Calcification leads to matrix hardening and eventual cell death (chondrocyte apoptosis).

• In the skeleton, this is a normal step in the transformation of cartilage into bone during development.

• In adults, pathologic calcification may occur, often contributing to cartilage degeneration (e.g., in osteoarthritis).