Watanabe Hideto
Institute for Molecular Science of Medicine, Aichi Medical University.
Clin Calcium. 2004 Jul;14(7):9-14.
The proteoglycan aggregate is the major structural component of the extracellular matrix of the cartilage, composed of aggrecan, hyaluronan (HA) and link protein (LP). The aggregates provide cartilage with unique gel-like property and resistance to deformation through water absorption. Natural knockout mice of aggrecan, termed cartilage matrix deficiency, and LP-null mice exhibit decreased levels of aggrecan depositon in cartilage and correspond well with their phenotypes such as dwarfism and spinal misalignment, demonstrating in vivo roles of the aggregate in cartilage development and homeostasis. Our recent studies demonstrate that versican/PG-M, another member of aggrecan family with a similar domain structure, binds both HA and LP, forming an aggregate. Further functional analyses of domains and subdomains showed distinct interaction of versican/PG-M with LP from aggrecan, suggesting that the versican/PG-M aggregate may have different function in cartilage.
蛋白聚糖聚集体是软骨细胞外基质的主要结构成分,由聚集蛋白聚糖、透明质酸(HA)和连接蛋白(LP)组成。这些聚集体通过吸水赋予软骨独特的凝胶样特性和抗变形能力。聚集蛋白聚糖的天然基因敲除小鼠(称为软骨基质缺陷小鼠)和LP基因缺失小鼠的软骨中聚集蛋白聚糖沉积水平降低,并且与它们的侏儒症和脊柱排列不齐等表型高度相符,这表明聚集体在软骨发育和稳态维持中具有体内作用。我们最近的研究表明,多功能蛋白聚糖/PG-M是聚集蛋白聚糖家族中另一个具有相似结构域结构的成员,它能同时结合HA和LP,形成聚集体。对结构域和亚结构域的进一步功能分析表明,多功能蛋白聚糖/PG-M与聚集蛋白聚糖的LP之间存在明显不同的相互作用,这表明多功能蛋白聚糖/PG-M聚集体在软骨中可能具有不同的功能。