A Short Basic Sciences Review of Articular Cartilage
Karen Luscombe and Francesco Oliva
Department of Trauma and Orthopaedic Surgery
Keele University School of Medicine
Hartshill, Thornburrow Drive
Stoke-on-Trent, Staffordshire, UK, ST4 7QB
Articular cartilage is a specialized connective tissue
covering joint surfaces that enables efficient function of the joints by
reducing friction and allowing load distribution. Macroscopically, it has a
glistening, white appearance. Microscopically, it is composed of water,
collagen, proteoglycans, chondrocytes and other matrix proteins and lipids. It
is avascular and alymphatic. It was also thought to be aneural, though recent
evidence suggests otherwise. The mechanisms of genetic regulation and
degeneration of articular cartilage are important to our understanding the
evolution of many degenerative and traumatic diseases.
Articular cartilage has been subdivided into five zones
depending on the alignment of collagen fibers, which give each zone particular
biomechanical advantages:
1. Superficial zone - resistant to shear
2. Transitional (middle) zone - resistant to compression
3. Radial (deep) zone - resistant to compression
4. Tidemark - resistant to shear
5. Calcified zone - acts as an anchor between articular cartilage and
subchondral bone
Chondrocytes
Chondrocytes are highly specialized mesenchymal cells, contributing 5% to the
whole weight and 1% to the volume of the articular cartilage. They are
responsible for the production of the structural components of articular
cartilage including collagen, proteoglycans and various enzymes. They are
located in lacunae, usually scattered individually throughout articular
cartilage. In arthritic cartilage, chondrocytes are recovered in clusters of up
to thirty cells, which probably represents an attempt at tissue regeneration.
During growth of the articular cartilage, chondrocytes have a constant, usually
roundish shape, but their shape becomes more variable depending on age,
pathological state and the cartilaginous layer to which they correspond. In the
superficial zone they are streamlined and orientated parallel to the articular
surface. In the intermediate zone they are spherical with a high metabolic
activity. In the deep zone the cells are large with small nuclei and are
arranged in perpendicular columns. Below in the zone of calcified cartilage
they appear as small, roundish cells with a large nucleus. The modification of
chondrocyte shape under load has been described and quantified using laser
microscopes.
The morphology of chondrocytes varies with changes in
osmotic pressure. In hypoosmotic conditions (120-150 mOsm), the plasma membrane
swells until eventually lysis occurs. In hyperosmotic conditions
(420mOsm), the cellular volume diminishes so the cell collapses on itself. In
physiological conditions (300-350 mOsm), the plasma membrane has microvilli,
which can be seen at electron microscopy, with a linear relationship between
the cellular volume and the osmolality.
Chondrocytes are anaerobic, and receive their nutrition
via diffusion of substances within synovial fluid, facilitated by movement of
this fluid during movement of the joint.
Intercellular Matrix
The intercellular matrix is composed of tissue fluid and structural
macromolecules, including collagens, proteoglycans, noncollagenic proteins and
glycoproteins. The relationship between these components determines the
characteristic biomechanical properties of articular cartilage.
It has a high water content of approximately 80%, which
is distributed nonuniformly (80% at the surface and 65% at the deep zone)
to allow deformation of the cartilage under stress. Higher water content is
found in the articular cartilage of patients with osteoarthritis, resulting in
an increase in permeability, decreased strength and fibrillation.
The collagens present in articular cartilage include
types II, VI, IX, X, XI, of which type II collagen represents 90-95%. Collagens
consist of a triple helix of ( chains twisted to form a superhelix. These align
in parallel rows with a quarter-staggered pattern; cross-linking of these
molecules also occurs. Collagen provides a structural framework that determines
the high tensile strength of cartilage. In the superficial zone fibrils are
oriented tangentially, in the intermediate zone fibrils are orientated
obliquely, and in the deep zone the fibrils are vertical. The function of type
VI collagen is still uncertain, though it may well stabilize chondrocytes
within the matrix. It is found in only small quantities in normal cartilage but
is greatly increased in osteoarthritis. Type X collagen is found in
hypertrophic cartilage, as seen in physes, fracture callus, or heterotopic
ossification.
Proteoglycans provide the compressive strength to the
articular cartilage and are composed of aggrecan molecules linked to hyaluronic
acid to form an aggregate macromolecule. Aggrecan molecules are composed of a
protein core with multiple glycosaminoglycans subunits. The glycosaminoglycans
include chondroitin-4-sulphate, chonroitin-6-sulphate and keratin sulphate. In
ageing, the level of chondroitin-4-sulphate decreases and that of keratin
sulphate increases. Non-collagenic proteins including anchorin C II,
fibronectin and chonronectin stabilize these proteoglycan macromolecules.
Regulation of Articular Cartilage Synthesis
Local factors are necessary for intercellular communications, and they include
cytokines and growth factors. A cytokine can be defined as a soluble low
molecular weight cell product that affects the activity of other local cells in
a paracrine manner. They may work on their cells of origin by an autocrine
mechanism, or, when released into the circulation, may affect cells at a
distant site, behaving as classic endocrine agents. In the bone and cartilage
another mechanism of control exists, where locally produced growth factors, or
those in the circulation, are incorporated into a mineralized matrix and are
released during matrix dissolution by osteoclasts or chondroclasts. There is
increasing evidence that abnormal production of cytokines in diseases such as
rheumatoid arthritis, osteoarthritis and osteoporosis may result in
inappropriate responses by bone and cartilage cells. Many articular cartilage
growth factors have been identified:
Insulin-like growth factors (IGF): IGF-I and II
Transforming growth factors (TGF): TGFßs 1-3
Fibroblast growth factors acidic and basic (aFGF and bFGF)
Interleukins(IL): IL-1ß; ?IL-6; IL-8
Tumor Necrosis Factors (TNF): TNF a
Colony stimulating factor (CSF): M-CSF
Others:Prostaglandins PTH-RP
Lubrication and Wear
The predominant method of lubrication of articular cartilage during joint
motion is elastohydrodynamic lubrication. This occurs when pressure in the
fluid film deforms the articular surface, increasing the surface area and
reducing escape of fluid from between the surfaces as they glide over each
other. Other methods of lubrication include boundary lubrication (in which a
lubricating glycoprotein prevents direct surface contact of the articulating
surfaces), boosted lubrication (where the solvent part of the lubricant enters
the articular cartilage which leaves the hyaluronic acid complxes acting as a
lubricant) and weeping lubrication (which describes the ability of articular
cartilage to exude or imbibe fluid as the joint surfaces glide over each other
providing self lubrication). The efficiency of these lubrication processes
means that wear in synovial joints is minimal.
Effects of Injury
Deep lacerations of articular cartilage extending
beyond the tidemark heal with fibrocartilage produced by undifferentiated
mesenchymal cells. Superficial lacerations do not heal, although some
proliferation of chondrocytes may occur. Immobilisation of joints leads to
atrophy of the articular cartilage and therefore continuous passive motion is
believed to be beneficial to healing.
Summary
The relationship of the composition of articular cartilage to its structural
integrity and function enhances our understanding of the effects of ageing,
degenerative diseases and injury to this tissue. Many articular cartilage
growth factors have been identified, but further investigation of the
mechanisms of genetic regulation of articular cartilage is required.
Manipulation of these processes may lead to future advances in the treatment of
degenerative diseases and injury.
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