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
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
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DOI：
10.1042/bj3300345
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发表时间：
1998-02-15
影响因子：
4.1
通讯作者：
Tekoppele, JM
中科院分区：
文献类型：
--
作者：
Bank, RA;Bayliss, MT;Tekoppele, JM
许多关于随着年龄增长而发生骨关节炎的假说都假定胶原网络的生物力学失效。在这里，我们研究了健康人体关节软骨中非酶糖化（NEG）产物的积累、其与组织重塑的关系及其在组织硬化中的作用。 20 岁之前戊糖素水平较低，此后呈线性上升。这表明年轻时发生广泛的组织重塑，而成熟后胶原蛋白的周转缓慢。胶原蛋白（羟赖氨酸、羟赖氨酰吡啶啉和赖氨酰吡啶啉）的酶促修饰与年龄无关的发现支持了缓慢的重塑。交联赖氨酰吡啶啉 (LP) 水平作为距关节表面距离的函数支持高度重塑。 LP 在成熟软骨（> 20 年）的表面最高，而在年轻软骨（< 10 年）中则相反；最高水平接近骨头。 14岁时软骨切片中的LP水平在表面和靠近骨骼处较高，但在中部区域较低。这表明软骨在生命的第二个十年开始成熟，从组织的上半部分开始，最后发生在靠近骨骼的组织中。研究了 NEG 产品对软骨瞬时变形的影响，作为体内戊糖素水平的地形变化的函数，并与体外诱导的 NEG 相关。一致地，较高的戊糖素水平与较硬的胶原蛋白网络相关。更硬、更交联的胶原蛋白网络可能会变得更脆并且更容易疲劳。
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 nonenzymatic 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.