Cartilagenous tissues are present throughout the body at numerous sites and are classified histologically as being hyaline, elastic or fibrocartilagenous in nature, depending on their molecular composition. Elastic cartilage is associated with the ear and the larynx, whereas fibrocartilage is associated with the menisci of the knee and the intervertebral discs. Hyaline cartilage is the predominant form of cartilage, and is most commonly associated with the skeletal system, where it forms the anlage for many bones in the embryo, the growth plate via which many bones increase their size during juvenile development, and the bearing surface upon which bones articulate in movable joints. It is not clear whether articular cartilage can be defined as a distinct tissue in the juvenile, as it forms a continuum with the hyaline cartilage of the central epiphysis, which is destined to be resorbed. Indeed, it is still somewhat of a mystery why articular cartilage survives at all and is not also replaced by bone.
At first sight, articular cartilage seems ill-equipped to deal with the constant mechanical insults to which it is exposed during normal joint function. It has no vascular system to provide nutrition and is only sparsely populated with cells, which are required to maintain the integrity of the vast extracellular matrix in regions that may be very remote. Some of these concerns are not applicable to the growth plate, which is penetrated by blood vessels and which possesses a higher cell density. However, the growth plate does have the additional problem of maintaining a precise columnar organization of its maturing cells to enable linear growth. The nutritional and repair problems of articular cartilage are magnified in the intervertebral discs, which in the lumbar spine are the largest avascular and least cellular tissues in the body. Nature’s solution to these problems resides in the unique structure of the extracellular matrix. In articular cartilage and intervertebral disc it provides the ability to resist compressive loading so protecting the cells from injury by mechanical trauma. In the growth plate, it provides the scaffold that maintains the unique cellular organization responsible for long bone elongation.
All hyaline cartilages are characterized by their high content of the proteoglycan aggrecan, which exists in the form of proteoglycan aggregates in association with hyaluronan (HA) and link protein (LP). The proteoglycan aggregates are responsible for the turgid nature of the cartilage and in articular cartilage they provide the osmotic properties needed to resist compressive loads. In common with all other connective tissues, cartilages also contain a variety of small leucine-rich repeat proteoglycans (SLRPs), which on a weight basis are a minor component of the tissue but on a molar basis may rival the abundance of aggrecan. Decorin, biglycan, fibromodulin and lumican are the major SLRPs present in cartilage, where they help maintain the integrity of the tissue and modulate its metabolism.
CS chondroitin sulphate
CS1/2 CS-rich domains of aggrecan
DS dermatan sulphate
EGF epidermal growth factor
G1-3 globular domains of aggrecan
HA hyaluronan (hyaluronic acid)
HAS hyaluronan synthase
IGD interglobular domain
KS keratan sulphate
LP link protein
LRR leucine-rich repeat
MMP matrix metalloproteinase
SLRP small leucine-rich repeat proteoglycan
TGF transforming growth factor
TNF tumor necrosis factor.