Asporin competes with decorin for collagen binding, binds calcium and promotes osteoblast collagen mineralization
Asporin competes with decorin for collagen binding, binds calcium and promotes osteoblast collagen mineralization
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DOI：
10.1042/bj20090542
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发表时间：
2009-10-01
影响因子：
4.1
通讯作者：
Oldberg, Ake
中科院分区：
文献类型：
--
作者：
Kalamajski, Sebastian;Aspberg, Anders;Oldberg, Ake
ECM（细胞外基质）蛋白与ECM成分的相互作用以前没有被研究过。在这里，我们发现了阿霉素结合i型胶原蛋白，这种结合被重组阿霉素片段LRR（富含亮氨酸的重复序列）10-12和全长decorin抑制，但不被biglycan抑制。我们证明了聚天冬氨酸结构域结合钙并调节羟基磷灰石的形成。在阿霉素的作用下，胶原结节数量增加，成骨细胞标志物Osterix和Runx2 mRNA表达增加。此外，decorin或胶原结合的天冬氨酸片段LRR 10-12抑制全长天冬氨酸的促成骨活性。我们的研究结果表明，在与胶原蛋白结合的过程中，天冬素和decorin相互竞争，而天冬素中的多天冬氨酸直接调节胶原蛋白矿化。因此，阿司匹林在成骨细胞驱动的胶原生物矿化活性中起作用。我们还发现，用正确定位的半胱氨酸桥可以在大肠杆菌（Rosettagami (TM)）中表达asporin，并且类似的系统可能用于表达其他slrp（小LRR蛋白聚糖/蛋白）。
The interactions of the ECM (extracellular matrix) protein asporin with ECM components have previously not been investigated. Here, we show that asporin binds collagen type I. This binding is inhibited by recombinant asporin fragment LRR (leucine-rich repeat) 10-12 and by full-length decorin, but not by biglycan. We demonstrate that the polyaspartate domain binds calcium and regulates hydroxyapatite formation in vitro. In the presence of asporin, the number of collagen nodules, and mRNA of osteoblastic markers Osterix and Runx2 were increased. Moreover, decorin or the collagen-binding asporin fragment LRR 10-12 inhibited the pro-osteoblastic activity of full-length asporin. Our results suggest that asporin and decorin compete for binding to collagen and that the polyaspartate in asporin directly regulates collagen mineralization. Therefore asporin has a role in osteoblast-driven collagen biomineralization activity. We also show that asporin can be expressed in Escherichia coli (Rosettagami (TM)) with correctly positioned cysteine bridges, and a similar system can possibly be used for the expression of other SLRPs (small LRR proteoglycans/proteins).