Age-related accumulation of Maillard reaction products in human articular cartilage collagen.
Age-related accumulation of Maillard reaction products in human articular cartilage collagen.
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DOI：
10.1042/bj3500381
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发表时间：
2000-09
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影响因子：
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通讯作者：
N. Verzijl;J. DeGroot;Esther Oldehinkel;R. Bank;S. Thorpe;J. Baynes;M. Bayliss;J. Bijlsma;
中科院分区：
文献类型：
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作者：
N. Verzijl;J. DeGroot;Esther Oldehinkel;R. Bank;S. Thorpe;J. Baynes;M. Bayliss;J. Bijlsma;
通过还原糖对组织蛋白质的非酶修饰，即所谓的美拉德反应，是衰老的一个显著特征。在关节软骨中，随着年龄的增长，相对高水平的晚期糖基化终产物（AGE）戊糖苷会积累。较高的戊糖苷水平与软骨中较硬的胶原蛋白网络有关。然而，即使在软骨中，戊糖苷水平本身也代表每20个胶原分子<1个交联，因此不能预期实质上有助于胶原网络刚度的增加。在本研究中，我们调查了广泛的美拉德反应产物在软骨胶原蛋白，以确定是否pentosidine作为一个足够的标记物AGE水平。不仅软骨胶原中的AGEs戊糖苷、N（N）-（羧甲基）赖氨酸和N（N）-（羧乙基）赖氨酸随着年龄的增长而增加（均P<0.0001），而且AGE交联的一般指标，如布朗宁和荧光（均P<0.0001）也增加。软骨胶原蛋白中这些AGEs的水平均高于皮肤胶原蛋白。作为糖化的功能措施的关节胶原蛋白的细菌胶原酶的消化率进行了研究，消化率随年龄呈线性下降，成比例的糖化程度。软骨胶原中精氨酸含量、羟赖氨酸和赖氨酸含量之和随年龄增长而显著降低（P<0.0001和P<0.0001）。01），可能是由于美拉德反应的改性。先前在体内尚未报道观察到的糖化和氨基酸修饰之间的关系。我们目前的研究结果表明，广泛积累的各种美拉德反应产物发生在软骨胶原随着年龄的增长。总之，我们的研究结果支持这一假设，糖化有助于更硬，更脆的软骨随着年龄的增长。
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 substantially 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(epsilon)-(carboxymethyl)lysine, and N(epsilon)-(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.