ISAKOS: Current Concepts: "A Short Basic Sciences Review of Articular Cartilage"


	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.