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Age-related accumulation of Maillard reaction products in human articular cartilage collagen

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Author: Verzijl, N. · Groot, J. de · Oldehinkel, E. · Bank, R.A. · Thorpe, S.R. · Baynes, J.W. · Bayliss, M.T. · Bijlsma, J.W.J. · Lafeber, F.P.J.G. · TeKoppele, J.M.
Institution: Gaubius Laboratory, Div. Vasc./Connective Tissue Res., TNO Prevention and Health, PO Box 2215, 2301 CE Leiden, Netherlands
Source:Biochemical Journal, 2, 350, 381-387
Identifier: 235646
doi: doi:10.1042/0264-6021:3500381
Keywords: Health Biology · Biomedical Research · Advanced glycation end product · Aging · Cross-linking · N(ε)-(carboxymethyl)lysine · Pentosidine · advanced glycation end product · arginine · collagen · collagenase · hydroxylysine · lysine · n carboxyethyllysine · n carxobymethyllysine · pentosidine · unclassified drug · adolescent · adult · age · aged · aging · amino acid composition · article · articular cartilage · bioaccumulation · child · color · controlled study · fluorescence · human · human tissue · priority journal · protein cross linking · protein degradation · protein glycosylation · skin · tensile strength · tissue level · Adolescent · Adult · Age Factors · Aged · Aged, 80 and over · Aging · Arginine · Cartilage, Articular · Child · Child, Preschool · Collagen · Collagenases · Cross-Linking Reagents · Female · Femur · Glycosylation End Products, Advanced · Humans · Lysine · Maillard Reaction · Male · Middle Aged · Skin · Spectrometry, Fluorescence


Non-enzymic modification of tissue proteins by reducing sugars, the so-called Maillard reaction, is a prominent feature of aging. In articular cartilage, relatively high levels of the advanced glycation end product (AGE) pentosidine accumulate with age. Higher pentosidine levels have been associated with a stiffer collagen network in cartilage. However, even in cartilage, pentosidine levels themselves represent < 1 cross-link per 20 collagen molecules, and as such cannot be expected to contribute sub-stantially to the increase in collagen network stiffness. In the present study, we investigated a broad range of Maillard reaction products in cartilage collagen in order to determine whether pentosidine serves as an adequate marker for AGE levels. Not only did the well-characterized AGEs pentosidine, N(ε)-(carboxymethyl)lysine, and N(ε)-(carboxyethyl)lysine increase with age in cartilage collagen (all P < 0.0001), but also general measures of AGE cross-linking, such as browning and fluorescence (both P < 0.0001), increased. The levels of these AGEs are all higher in cartilage collagen than in skin collagen. As a functional measure of glycation the digestibility of articular collagen by bacterial collagenase was investigated; digestibility decreased linearly with age, proportional to the extent of glycation. Furthermore, the arginine content and the sum of the hydroxylysine and lysine content of cartilage collagen decrease significantly with age (P < 0.0001 and P < 0.01 respectively), possibly due to modification by the Maillard reaction. The observed relationship between glycation and amino acid modification has not been reported previously in vivo. Our present results indicate that extensive accumulation of a variety of Maillard reaction products occurs in cartilage collagen with age. Altogether our results support the hypothesis that glycation contributes to stiffer and more brittle cartilage with advancing age.