AGING AND ZONAL VARIATION IN POSTTRANSLATIONAL MODIFICATION OF COLLAGEN IN NORMAL HUMAN ARTICULAR-CARTILAGE - THE AGE-RELATED INCREASE IN NONENZYMATIC GLYCATION AFFECTS BIOMECHANICAL PROPERTIES OF CARTILAGE

A biomechanical failure of the collagen network is postulated in many hypotheses of the development of osteoarthritis with advancing age. He re we investigate the accumulation of nonenzymatic glycation (NEG) pro ducts in healthy human articular cartilage, its relation to tissue rem odelling and its role in tissue stiffening. Pentosidine levels were lo w up to age 20 years, and increased linearly after this age. This indi cates extensive tissue remodelling at young age, and slow turnover of collagen after maturity has been reached. The slow remodelling is supp orted by the finding that enzymatic modifications of collagen (hydroxy lysine, hydroxylysylpyridinoline, and lysylpyridinoline) were not rela ted to age. The high remodelling is supported by levels of the crossli nk lysylpyridinoline (LP) as a function of distance from the articular surface. LP was highest at the surface in mature cartilage (> 20 year s), whereas in young cartilage (< 10 years) the opposite was seen; hig hest levels were close to the bone. LP levels in cartilage sections at age 14 years are high at the surface and close to the bone, but they are low in the middle region. This indicates that maturation of cartil age in the second decade of life starts in the upper half of the tissu e, and occurs last in the tissue close to the bone. The effect of NEG products on instantaneous deformation of cartilage was investigated as a functional of topographical variations in pentosidine levels in viv o and in relation to in vitro induced NEG. Consistently, higher pentos idine levels were associated with a stiffer collagen network. A stiffe r and more crosslinked collagen network may become more brittle and mo re prone to fatigue.