Ageing and zonal variation in post-translational modification of collagen in normal human articular cartilage:​ the age-related increase in non-enzymatic glycation affects biomechanical properties of cartilage

Bank, Ruud A.; Bayliss, Michael T.; Lafeber, Floris P. J. G.; Maroudas, Alice; Tekoppele, Johan M.

Affiliations

¹Gaubius Laboratory TNO Prevention and Health, Division of Vascular and Connective Tissue Research, P.O. Box 2215, 2301 CE Leiden, The Netherlands

²Department of Veterinary Basic Sciences, The Royal Veterinary College (University of London), Royal College Street, London NW1 OTU, U.K.

³Department of Rheumatology and Clinical Immunology, University Hospital Utrecht, P.O. Box 85500, 3508 GA Utrecht, The Netherlands

⁴Julius Silver Institute of Biomedical Science and Department of Biomedical Engineering, Technion (Israel Institute of Technology), Haifa 32000, Israel

Abstract

A biomechanical failure of the collagen network is postulated in many hypotheses of the development of osteoarthritis with advancing age. Here we investigate the accumulation of non-enzymatic glycation (NEG) products in healthy human articular cartilage, its relation to tissue remodelling and its role in tissue stiffening. Pentosidine levels were low up to age 20 years, and increased linearly after this age. This indicates extensive tissue remodelling at young age, and slow turnover of collagen after maturity has been reached. The slow remodelling is supported by the finding that enzymatic modifications of collagen (hydroxylysine, hydroxylysylpyridinoline, and lysylpyridinoline) were not related to age. The high remodelling is supported by levels of the crosslink lysylpyridinoline (LP) as a function of distance from the articular surface. LP was highest at the surface in mature cartilage (> 20 years), whereas in young cartilage (< 10 years) the opposite was seen; highest 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 cartilage in the second decade of life starts in the upper half of the tissue, 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 vivo and in relation to in vitro induced NEG. Consistently, higher pentosidine levels were associated with a stiffer collagen network. A stiffer and more crosslinked collagen network may become more brittle and more prone to fatigue.

Links

DOI: 10.1042/bj3300345

PubMed: 9461529

WoS: 000072441800049

History

Received: 1997-05-27

Revised: 1997-10-10

Accepted: 1997-10-24

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