Allen Justin M, Bateman John F, Hansen Uwe, Wilson Richard, Bruckner Peter, Owens Rick T, Sasaki Takako, Timpl Rupert, Fitzgerald Jamie
Cell and Matrix Biology Research Unit, Murdoch Childrens Research Institute and Department of Paediatrics, University of Melbourne, Royal Children's Hospital, Flemington Road, Parkville, Victoria 3052, Australia.
J Biol Chem. 2006 Mar 17;281(11):7341-9. doi: 10.1074/jbc.M513746200. Epub 2006 Jan 6.
WARP is a novel member of the von Willebrand factor A domain superfamily of extracellular matrix proteins that is expressed by chondrocytes. WARP is restricted to the presumptive articular cartilage zone prior to joint cavitation and to the articular cartilage and fibrocartilaginous elements in the joint, spine, and sternum during mouse embryonic development. In mature articular cartilage, WARP is highly specific for the chondrocyte pericellular microenvironment and co-localizes with perlecan, a prominent component of the chondrocyte pericellular region. WARP is present in the guanidine-soluble fraction of cartilage matrix extracts as a disulfide-bonded multimer, indicating that WARP is a strongly interacting component of the cartilage matrix. To investigate how WARP is integrated with the pericellular environment, we studied WARP binding to mouse perlecan using solid phase and surface plasmon resonance analysis. WARP interacts with domain III-2 of the perlecan core protein and the heparan sulfate chains of the perlecan domain I with K(D) values in the low nanomolar range. We conclude that WARP forms macromolecular structures that interact with perlecan to contribute to the assembly and/or maintenance of "permanent" cartilage structures during development and in mature cartilages.
WARP是细胞外基质蛋白的血管性血友病因子A结构域超家族的一个新成员，由软骨细胞表达。在小鼠胚胎发育过程中，关节腔形成之前，WARP局限于假定的关节软骨区，在关节、脊柱和胸骨中则局限于关节软骨和纤维软骨成分。在成熟的关节软骨中，WARP对软骨细胞周围微环境具有高度特异性，并与软骨细胞周围区域的主要成分基底膜聚糖共定位。WARP以二硫键结合的多聚体形式存在于软骨基质提取物的胍可溶性部分，表明WARP是软骨基质的一个强相互作用成分。为了研究WARP如何与细胞周围环境整合，我们使用固相和表面等离子体共振分析研究了WARP与小鼠基底膜聚糖的结合。WARP与基底膜聚糖核心蛋白的III-2结构域以及基底膜聚糖结构域I的硫酸乙酰肝素链相互作用，解离常数（K(D)）值在低纳摩尔范围内。我们得出结论，WARP形成与基底膜聚糖相互作用的大分子结构，有助于在发育过程中和成熟软骨中组装和/或维持“永久性”软骨结构。
