The Oxford Science Lecture Series

DR JILL URBAN

Department of Physiology, University of Oxford

"Cartilage and your joints - from cradle to grave"

University Museum, Oxford, 4th December 2001

Is life worth living? According to Dr. Jill Urban of the Department of Physiology, Oxford University, that depends not upon the liver but upon the condition of the cartilages in one's joints. This was no narrow-minded outlook on the importance of one's own research: the quality of cartilage material that we carry through life in our skeletons is basically what we were born with. Statistically, skeletal problems are one of the most common causes of pain in humans, and the cartilage is at the heart of it all. It was fascinating to delve into the reasons.

Cartilage occurs throughout the skeleton wherever bones move across one another. Its function is to cushion joints and to allow the spine to bend; its rubbery texture can absorb a great deal of mechanical stress - as much as five times body weight in the hips, for instance. The two main forms of cartilage that occur in the skeleton are articular cartilage, which is found at the end of long bones (fingers, legs, arms), and disk cartilage, which is sited between vertebrae. A disk - about 8 cm across and more than 1 cm thick - consists mainly of collagen fibres embedded in a stiff gel of proteoglycans; other compounds attached to the outside of the proteoglycan molecule are present in minor amounts. Whilst the components of the different types of cartilage are broadly the same, their structures are not; in articular cartilage the collagen fibres anchor the cartilage to the end of a bone, whereas in disk cartilage they are formed in annular rings running from one vertebral body to the next. Embedded in the collagen/proteoglycan matrix are cells which generate matrix to balance degradation. Cells are relatively few in number and they do not multiply. Their metabolism is normally rather low, but is raised in response to external forces; their generation of matrix is affected by mechanical load. Cartilages have no blood vessels, but take their meagre ration of nutrients by diffusion from the synovial fluid or, in the case of a disc, from the blood vessels in the adjacent bone. Nutrients, waste products, chemical messengers and hormones are then transported to the cells through the soft matrix. Thus even in a normally healthy cartilage there are steep gradients of oxygen concentrations from edge to middle; any calcification at the edge of the cartilage can severely restrict the supply of nutrients.

The proteoglycans are osmotic, and the cartilage matrix absorbs water freely; between 60 and 80% of a cartilage is actually water, the amount varying according to joint type. If a disk cartilage is put into saline solution it will swell to three or four times its volume, especially the soft area in the middle. In the body, its water content is maintained by body weight and muscles; when under pressure it loses significant amounts of water, and regains it during rest. For this reason, people leading a conventional life tend to shrink slightly during the day - maybe 1 or 2 cm - but regain that height as the disks swell again during the night. Astronauts experiencing a condition of weightlessness may become taller by as much as 5 cm.

As joints and tissues age, proteoglycan concentrations fall and cartilage becomes more compressible, affecting its performance and reducing its cushioning capability. Joint surfaces then become irregular, and bone-to-bone contact and degenerative arthritis can result. The precise mechanisms of cartilage breakdown are not well understood, though new techniques to research the causes are being pursued. In cases of injury, the current outlook is also not very cheerful. Because of the curious structure of cartilage, complete natural repair of a cartilage injury is unlikely. Proteoglycan levels are never fully restored to their originals, and once-damaged joints tend to become arthritic sooner than they would through ordinary wear and tear. Curiously, the degree of associated pain is not necessarily correlated with the seriousness of an injury; damaged spinal disks can be excruciatingly painful and debilitating, or can be accommodated with little or no pain even when badly distorted. At present surgery is the only really successful treatment for all joint disorders, though it may only be a short-term solution: artificial joints remove pain and restore mobility, but they usually wear out after about 15 years. Tissue engineering, gene therapy and drug treatments are not yet practical solutions, but all are under development.

Joint diseases and damage may not be life-threatening, but they certainly make life painful for most of us in due course, one way or another. The ageing and deterioration of cartilage actually sets in by age 20! It is well known that back problems are the most frequent cause of absences from work, yet despite the considerable economic implications only a small fraction of UK research effort is directed towards alleviating joint problems. But that may yet change: 2000-2010 is the Bone and Joint Decade, set up by the World Health Organization with the aims of raising awareness of the burdens that musculoskeletal disorders place on society, promoting cost-effective treatment, and advancing understanding of such disorders through research. Dr. Urban's lucid lecture left us in no doubt that here, at least, was one researcher doing something extremely worthwhile.

Dr Elizabeth Griffin