The human lumbar intervertebral disc - Evidence for changes in the biosynthesis and denaturation of the extracellular matrix with growth, maturation, ageing, and degeneration
The human lumbar intervertebral disc - Evidence for changes in the biosynthesis and denaturation of the extracellular matrix with growth, maturation, ageing, and degeneration
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DOI：
10.1172/jci118884
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发表时间：
1996-08-15
影响因子：
15.9
通讯作者：
Alini, M
中科院分区：
文献类型：
--
作者：
Antoniou, J;Steffen, T;Alini, M
我们测量了121个人类腰椎间盘预定区域中反映基质合成和降解的特定分子的浓度，并将它们与衰老和汤普森级退变相关联。通过免疫分析法测定推定的聚集蛋白生物合成标志物（846）的含量以及I型和II型前胶原标志物的含量，在新生儿和2-5岁年龄组中最高。随着年龄的增长，这些表位/分子的含量逐渐减少。然而，在年龄最大的年龄组（60-80岁）和高度退变的椎间盘中，I型前胶原表位水平显著升高。变性II型胶原的百分比，通过II型胶原切割暴露的表位的存在来评估，从新生儿椎间盘到年轻的2-5岁年龄组增加了两倍。此后，随着年龄的增长，该比例逐渐降低；我们确定了三个基质周转阶段，第一阶段（生长）的特征是基质分子的活跃合成和II型胶原蛋白的活跃变性，第二阶段（成熟和衰老）的特征是合成活性的逐渐下降和II型胶原蛋白变性的逐渐减少。III期（变性和纤维化）表现为聚集蛋白和II型前胶原合成缺乏增加，但也表现为II型变性胶原和I型前胶原合成增加，这两者都取决于年龄和组织变性的程度。
Very little is known about the turnover of extracellular matrix in the human intervertebral disc, We measured concentrations of specific molecules reflecting matrix synthesis and degradation in predetermined regions of 121 human lumbar intervertebral discs and correlated them with ageing and Thompson grade of degeneration,Synthesis in intervertebral discs, measured by immunoassay of the content of a putative aggrecan biosynthesis marker (846) and the content of types I and II procollagen markers, is highest in the neonatal and 2-5-yr age groups. The contents of these epitopes/molecules progressively diminished with increasing age. However, in the oldest age group (60-80 yr) and in highly degenerated discs, the type I procollagen epitope level increased significantly.The percentage of denatured type II collagen, assessed by the presence of an epitope that is exposed with cleavage of type II collagen, increased twofold from the neonatal discs to the young 2-5-yr age group. Thereafter, the percentage progressively decreased with increasing age; however, it increased significantly in the oldest group and in highly degenerate discs, We identified three matrix turnover phases, Phase I (growth) is characterized by active synthesis of matrix molecules and active denaturation of type II collagen, Phase Ii (maturation and ageing) is distinguished by a progressive drop in synthetic activity and a progressive reduction in denaturation of type II collagen, Phase III (degeneration and fibrotic) is illustrated by evidence for a lack of increased synthesis of aggrecan and type II procollagen, but also by an increase in collagen type II denaturation and type I procollagen synthesis, both dependent on age and grade of tissue degeneration.