Roughley P, Martens D, Rantakokko J, Alini M, Mwale F, Antoniou J
Shriners Hospital for Children, Department of Surgery, McGill University, Montreal, Quebec, Canada.
Eur Cell Mater. 2006 Jan 18;11:1-7; discussion 7.
The functions of the intervertebral disc and of articular cartilage are intimately related to their aggrecan content. Aggrecan is a proteoglycan that interacts with hyaluronan to form large aggregates, which are responsible for the ability of the tissues to resist compressive loads. This function is related to the structure of aggrecan, and in particular to the large number of chondroitin sulphate chains present on its core protein. The chondroitin sulphate chains are present in two adjacent regions of the aggrecan core protein, termed the CS1 and CS2 domains. In the human, the region of the aggrecan gene encoding the CS1 domain exhibits size polymorphism, which can result in variation in the degree of chondroitin sulphate substitution of aggrecan in different individuals. This raises the possibility that the functional properties of aggrecan may vary between individuals, and that those individuals with an inferior aggrecan structure may be more susceptible to premature intervertebral disc or articular cartilage degeneration. Several studies have been performed to demonstrate such an association, but the results have been ambiguous. This review explains the relationship between aggrecan structure and function, describes the technique used to assess aggrecan polymorphism and the conclusions and limitations of the data obtained to date, and discusses the implications for tissue degeneration and clinical practice.
椎间盘和关节软骨的功能与其聚集蛋白聚糖含量密切相关。聚集蛋白聚糖是一种蛋白聚糖，它与透明质酸相互作用形成大的聚集体，这些聚集体赋予组织抵抗压缩负荷的能力。该功能与聚集蛋白聚糖的结构有关，特别是与其核心蛋白上存在的大量硫酸软骨素链有关。硫酸软骨素链存在于聚集蛋白聚糖核心蛋白的两个相邻区域，称为CS1和CS2结构域。在人类中，聚集蛋白聚糖基因编码CS1结构域的区域表现出大小多态性，这可能导致不同个体中聚集蛋白聚糖硫酸软骨素取代程度的差异。这增加了聚集蛋白聚糖的功能特性可能在个体之间有所不同的可能性，并且那些聚集蛋白聚糖结构较差的个体可能更容易发生椎间盘或关节软骨过早退变。已经进行了几项研究来证明这种关联，但结果并不明确。这篇综述解释了聚集蛋白聚糖结构与功能之间的关系，描述了用于评估聚集蛋白聚糖多态性的技术以及迄今为止获得的数据的结论和局限性，并讨论了对组织退变和临床实践的影响。
