Bank R A, Verzijl N, Lafeber F P J G, Tekoppele J M
Gaubius Laboratory TNO Prevention and Health, Leiden, The Netherlands.
Osteoarthritis Cartilage. 2002 Feb;10(2):127-34. doi: 10.1053/joca.2001.0487.
The collagen network in human articular cartilage experiences a large number of stress cycles during life as it shows hardly any turnover after adolescence. We hypothesized that, to withstand fatigue failure, the physical condition of the collagen network laid down at adolescence is of crucial importance for the age of onset of osteoarthritis (OA).
We have compared the lysyl hydroxylation level and pyridinoline cross-link level of the collagen network of degenerated (DG) cartilage of the femoral knee condyle (representing a preclinical early stage of OA) with that of normal cartilage from the contralateral knee. The biological age of the collagen network was determined by means of pentosidine levels. For each donor, collagen modifications of normal cartilage were compared with DG cartilage that showed no significant remodeling of the collagen network (as evidenced by identical pentosidine levels).
DG cartilage contained significantly more hydroxylysine residues per collagen molecule in comparison with healthy cartilage from the same donor, both in the upper and lower half (the region near the articular surface and adjacent to bone, respectively). In addition, a significantly higher level of pyridinoline cross-linking was observed in the upper half of DG cartilage. Considering the biological age of the collagen network, the changes observed in DG cartilage must have been present several decades before cartilage became degenerated.
The data suggest that high levels of lysyl hydroxylation and pyridinoline cross-linking result in a collagen network that fails mechanically in long term loading. Areas containing collagen with low hydroxylysine and pyridinoline levels are less prone to degeneration. As such, this study indicates that post-translational modifications of collagen molecules synthesized during adolescence are causally involved in the pathogenesis of OA.
人类关节软骨中的胶原网络在一生中经历大量应力循环，因为青春期后其几乎没有更新。我们推测，为了承受疲劳破坏，青春期形成的胶原网络的物理状态对于骨关节炎（OA）发病年龄至关重要。
我们比较了股骨髁退化（DG）软骨（代表OA临床前期早期阶段）的胶原网络的赖氨酰羟化水平和吡啶啉交联水平与对侧膝关节正常软骨的相应水平。通过戊糖苷水平确定胶原网络的生物学年龄。对于每个供体，将正常软骨的胶原修饰与胶原网络未显示明显重塑的DG软骨（由相同的戊糖苷水平证明）进行比较。
与同一供体的健康软骨相比，DG软骨在每个胶原分子中含有明显更多的羟赖氨酸残基，在上半部分和下半部分（分别靠近关节表面和邻近骨骼的区域）均是如此。此外，在DG软骨的上半部分观察到明显更高水平的吡啶啉交联。考虑到胶原网络的生物学年龄，在软骨退化前几十年就必定已经出现了DG软骨中观察到的变化。
数据表明，高水平的赖氨酰羟化和吡啶啉交联导致胶原网络在长期负荷下发生机械性失效。含有低水平羟赖氨酸和吡啶啉的胶原区域不易发生退化。因此，本研究表明青春期合成的胶原分子的翻译后修饰在OA发病机制中起因果作用。
