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Osteoarthritis (OA) is one of the most prevalent diseases of the elderly, affecting greater than 50% of the population over 60 years of age. Many factors are implicated in the development of OA but currently no mechanism has been described that provides an explanation for age as the major risk factor for OA. The present studies were designed to investigate the hypothesis that age-related accumulation of advanced glycation endproducts (AGEs) provides a molecular mechanism that explains (at least in part) the age-related increase in the incidence of OA.

To gain insight in the diversity of AGEs present in articular cartilage, several AGE measures were determined in a wide age-range of normal human articular cartilage samples: all demonstrated increased AGE levels with increasing age. The level of these AGEs was high in cartilage compared to other tissues such as skin, which is mainly caused by the very low turnover of the cartilage matrix proteins. The t1/2 of collagen in articular cartilage is ~117 years (compared to t1/2 of skin collagen of ~15 years).

Accumulation of AGEs in cartilage affected biomechanical, biochemical and cellular characteristics of the tissue. At the biomechanical level, increased AGE levels were accompanied by increased stiffness and brittleness, indicating that AGE accumulation leads to increased susceptibility of articular cartilage to mechanical damage. On the cellular level, accumulation of AGEs decreased the synthesis and degradation (= turnover) of the cartilage matrix. Such decreased cartilage turnover is likely to result in decreased repair capacity of the tissue.

In combination, the AGE-related increase in tissue brittleness and decrease in extracellular matrix turnover, results in articular cartilage that is more prone to damage. This concept, that AGE accumulation predisposes to the development of OA was tested in the canine anterior cruciate ligament transection (ACLT) model for osteoarthritis. Selectively enhancing AGE levels in articular cartilage of young animals (in the absence of other age-related changes) resulted in more severe OA.

Altogether, AGE accumulation in articular cartilage presents a molecular mechanism by which ageing predisposes to the development of OA, and it provides new possibilities for prevention and/or therapy via the inhibition and/or reversal of cartilage AGE formation.

The abstracts were prepared by Dr C Pither. Correspondence should be addressed to him at the British Orthopaedic Association, Royal College of Surgeons, 35–43 Lincoln’s Inn Fields, London WC2A 3PN