ARTICULAR
CARTILAGE
STRUCTURE, INJURY & HEALING
Nadhaporn Saengpetch
Division of Sports Medicine,
Department of Orthopaedics,
Faculty of Medicine Ramathibodi Hospital,
Mahidol University
COMPOSITION
• Extracellular matrix
and sparse cells
• No blood vessel,
lymphatic vessel
and nerve
• limit response to
any metabolic
response
• Frictionless
CHONDROCTYE
• Endoplasmic
reticulum and Golgi
apparatus (matrix
synthesis)
• Intracytoplasmic
filament, lipid,
glycogen, secretary
vesicles
(maintenance of
matrix structure)
CHONDROCYTE: DIFFERENT BY
LAYERS
• Surface layer:
elongated and
resemble fibroblasts
• Transitional layer:
round and actively for
chemistry
• Deeper layer:
cells in radial pattern
• Tidemark:
non-functional cells
COLLAGEN FIBRILS
CHONDROCYTE: FUNCTION
• NOT participate in water distribution
• Maintenance and structural competence
• Producing and replacing appropriate
macromolecules (degradation, mechanical
demand placed on the surface,
synthesizing)
• Assembling as an highly
ordered framework
CARTILAGE ZONES
EXTRACELLULAR MATRIX (ECM)
• 2 components
1. Tissue fluid
2. Framework of
structural
macromolecule
• Interaction ->
stiffness and
resilience
ECM
• Water 80% by weight
• Gel forming = lubrication system
• Large aggregation of Proteoglycans
(maintain fluid within the matrix and
e’lyte concentration)
ECM MOVEMENT
Na+
Cl
Cl
-
Na+
-
STRUCTURAL
MACROMOLECULES
STRUCTURAL
MACROMOLECULES
• Collagens
• Proteoglycans
• Noncollagenous
proteins
20-40% wet wt.
Glycoprotein
15%
Proteoglycan
25%
Collagen
60%
COLLAGEN
•
•
•
•
60% of dry weight of cartilage
Collagen-rich superficial zone
Types: II*, VI, IX, X and XI
Type II, IX and XI form the cross-band
fibrils
TIGHT MESHWORK
Collagen fibrils
organization
Large proteoglycans
entrapment
Tensile stiffness &
cartilage strength
Cohesiveness of tissue
TYPE II COLLAGEN
• 90-95% of cartilage
collagen
• The primary
component of
cross-banded fibrils
TYPE VI COLLAGEN
• Forms an important
part of surrounding
chondrocytes
• Helps chondrocyte
attach to matrix
TYPE IX COLLAGEN
• Bind covalently to
superficial layers of
cross-banded
fibrils
• Project into the
matrix to bind with
other Type IX
Collagen and
Proteoglycans
TYPE X
COLLAGEN
TYPE XI
COLLAGEN
• Found only near
• Bind covalently to
cartilage calcified
Type II
zone and
•
May
form
part
of
hypertrophic zone
interior structure of
of growth plate
cross-banded fibrils
(start to mineralize)
• Cartilage
mineralization
PROTEOGLYCANS
• A protein core &
Glycosaminoglycans
(GAG) chains
(unbranched
polysaccharide)
• GAG: Hyaluronic
acid, chondroitin
sulfate, glucosamine
sulfate, dermatan
sulfate
ARTICULAR
PROTEOGLYCAN
Aggrecans*
(large)
Decorin
Biglycan
Fibromodulin
(small)
AGGRECANS
•
•
•
•
Mostly fill in the interfibrillar space of matrix
90% of Pg mass
Noncovalently bind with HA & monomer
Help anchor Pg in the matrix, prevent
displacement during deformation, organize
and stabilize Pg & collagen
DECORINS
• One dermatan
sulfate chain
BIGLYCAN & FIBROMODULIN
Biglycan
• Two dermatan
sulfate chains
Fibromodulin
• Several dermatan
sulfate chains
ARTICULAR
PROTEOGLYCAN
Aggrecans*
(large)
- Healing
+ Degradative
enzymes
Transforming
growth factor β
Decorin
Biglycan
Fibromodulin
(small)
HYALURONIC ACID
• Backbone for matrix aggregation
• Bind aggrecans non-covalently and link proteins
• This aggregation helps anchor Pg within the
matrix
• Prevent displacement during deformation
• Stabilize relationships of Pg and collagen
meshwork
NONCOLLAGENOUS PROTEINS
& GLYCOPROTEINS
• Stabilize the matrix framework
• Help chondrocytes bind to the
macromolecules of matrix
• Anchorin CII collagen-binding
chondrocytes surface protein (anchor)
• Cartilage oligomeric protein (COMP) is in
chondrocyte territorial matrix, have
capacity to bind to chondrocyte
ZONES OF ARTICULAR
CARTILAGE
SUPERFICIAL ZONE
• Thinnest zone
• Two sub layers:
– sheet of fine fibrils (acellular)
– flattened ellipsoid-shape chondrocyte +
fibroblast
• Collagen is lying parallel to the joint
surface (resist compressive force)-> OA
• High collagen, low Pg
• “cartilage skin”
TRANSITIONAL ZONE
• Large volume
• cells: synthetic organelles (ER, Golgi)
spheroidal shape
• Lower collagen & water concentration
• Higher Pg concentration
MIDDLE(RADIAL/DEEP) ZONE
• Chondrocytes align in columns
perpendicular to the joint surface (resist
shear stress)
• Largest diameter collagen
• Highest Pg
• Lowest water
• Collagen fibers pass into the tidemark
CALCIFIED CARTILAGE ZONE
• Thin calcified cartilage
• “calcific sepulchers”
• Extremely low level of
metabolic activity
• No nutrients traverse this
zone
MATRIX REGIONS
• Pericellular
• Territorial
• Bind cell membranes to
matrix macromolecules
• Protect deformation force
• Transmit mechanical
signals to chondrocytes
• Interterritorial >>>
• Provide the mechanical
properties of tissue
CHONDROCYTE-MATRIX
INTERACTIONS
• Matrix protects chondrocytes from mechanical
damage and maintain shape and phenotype
• Matrix : metabolic products/cytokines and growth
factors
• Insulin-dependent growth factor I (IGF-I) &
Transforming growth factor β (TGF β) + matrix
synthesis & cell proliferation
CHONDROCYTE-MATRIX
INTERACTIONS
+
IGF-I
TGF β
BIOMECHANICS
Tension
Compression
Shear
• Wide range of static &
dynamic mechanical
loads
• Compressive, tensile
& shear forces
α composition &
structure of ECM
TENSILE & SHEAR FORCE
• These forces are
resisted by ropelike collagen fibrils
COMPRESSIVE FORCE
• Resisted by highly charged GAG such
as aggrecan molecules
LOADING vs IMMOBILIZATION
Induced wide range
of metabolic
response
Decreased in matrix
synthesis
CARTILAGE REGENERATION
Static compression
Cyclical compressive
Reversibly inhibit
cartilage matrix
synthesis
Stimulate aggrecan
core protein &
protein synthesis
DEGENERATION AND
OSTEOARTHRITIS
• Osteoarthritis >> degenerative joint
disease, degenerative arthritis,
hypertrophic arthritis
HOW THEY CHANGE?
OA: 3 OVERLAPPING PROCESSES
1. Cartilage matrix damage
2. Chondrocyte response to tissue damage
3. Decline of the chondrocyte synthetic
response
STAGE 1 MATRIX DAMAGE
Water
Aggrecan & GAG
length
Permeability
& Matrix stiffness
Other causes: inflammation, tissue’s metabolic
changes that interferes matrix maintenance
STAGE 2
CHONDROCYTE RESPONSE
• Chondrocytes
detect tissue
damage
Catabolic enzymes
(proteases)
Anabolic & mitogenic
growth factors
+ chondrocyte
proliferation & ECM
Reversible
- Spontaneous
- Intervention
STAGE 3
DECLINE CELL SYNTHESIS
• Failure to restore
the tissue
• Progressive loss of
cartilage
• Down regulation of
chondrocyte
response to
anabolic cytokine
JOINT INJURY &
POSTTRAUMATIC OA
• Ligament reconstruction (ex. ACL-R) can
restore mechanical stability but not greatly
reduce the risk for OA development
because….
The initial traumatic event may have
irreversible effects on the joint tissues and
residents cells
Good Luck