Quick Dips

Under Pressure

Allan Coukell, Auckland

Pity your knees, especially the cartilage that covers the ends of your bones. Most of the time, this tough, slippery tissue protects your joints rather well. But when cartilage is damaged by osteoarthritis, the result is pain and disability. Now, a new understanding of how normal cartilage functions may lead to effective treatments for damaged joints.

Cartilage acts like the cushioning on a plush chair, absorbing compressive forces and transferring the load to the underlying frame -- your bones. An intricate mesh-work of fibrous proteins, called collagens, gives shape to the tissue, while large "spongy" molecules known as proteoglycans act as the stuffing, causing the cartilage to swell and giving it an elastic resistance to compression. Under a load (such as the force on your knees when you stand up), the cartilage matrix is deformed, and water is squeezed out of the tissue. When the load is removed, the cartilage returns to its normal shape. These changes allow the cartilage to cushion your steps all day long.

The collagen and proteoglycan are synthesised and maintained by cells, called chondrocytes, which exist in relatively small numbers within the cartilage. The production of cartilage by chondrocytes occurs very, very slowly, and the cells rarely undergo cell division. Nevertheless, under normal circumstances, chondrocytes are able to sustain the cartilage for the lifetime of the joint.

Dr Tony Poole, a researcher at the University of Auckland, studies chondrocytes. He has shown that the surface of the chondrocyte is linked to nearby components of the cartilage matrix, so that each cell effectively sits enclosed in a tightly woven cocoon-like capsule.

The combination of cell and capsule, called a chondron, was first described in 1925, but Poole has recently demonstrated that the chondron functions as a distinct anatomical unit within the cartilage. He postulates that the tough, relatively impermeable capsule of the chondron serves to protect the enclosed chondrocyte from the constant physical distortion and rapid movement of water that the matrix undergoes. This may have implications for the future treatment of osteoarthritis (OA).

Although the exact causes of OA are unclear, the general pattern of its development is well known. An abnormal stress (either a single, sudden injury or repeated minor stresses) causes an alteration in the cartilage surface. Enzymes are then able to penetrate the tissue, causing further erosion. Often, deep fissures extend into the underlying bone. Joint motion becomes painful. Although chondrocytes cluster around these fissures, they are rarely able to synthesise sufficient normal cartilage to replace the damaged tissue.

Unfortunately, medical treatment of OA is still mostly focused on controlling pain. Attempts at surgical repair of cartilage rarely result in the production of useful new tissue. In very severe OA, the only option may be to replace the whole joint with an artificial prosthesis. However, artificial joints have a limited lifespan and thus are impractical in young patients. What is needed is a way to stimulate the damaged cartilage to repair itself.

One strategy is to extract chondrocytes from an undamaged region of cartilage, culture them in the laboratory, and then introduce the new cells into the damaged areas of the joint. There, it is hoped the new chondrocytes will attach to the old matrix, filling the defect with replacement cartilage.

Several researchers, including Dr Mats Brittberg, at the University of Gothenburg, in Sweden, have demonstrated promising results using this procedure. Brittberg has shown that transplanted chondrocytes are able to produce normal cartilage, at least in some patients. The main problem with all of the experiments so far is that the repair tissue tends to heal incompletely with the adjacent cartilage.

Poole thinks that the trouble might lie, at least in part, with the way chondrocytes are usually grown in culture. The process involves removing the cells from the cartilage and allowing them to multiply as a single layer of cells in a plastic dish. However, this tends to alter the behaviour of the cells, reducing their ability to produce a normally functioning matrix.

Poole and his colleagues are now working on better ways to extract and culture chondrocytes. They've shown that cells grown in three-dimensional gel cultures produce a more chondron-like matrix than monolayer cultures. The Auckland researchers believe cells grown in this way could improve the outcome of cartilage transplants. Poole hopes to test his theory beginning with studies in animals next year.

Routine cartilage transplants are probably still years away. But, transplanting laboratory-grown chondrocytes may one day prove to be a cheaper and better treatment for OA than those available today. Now, that should put the spring back in your step.

Allan Coukell is a freelance medical and science writer based in Auckland.