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Perlecan domain 1 recombinant proteoglycan augments BMP-2 activity and osteogenesis

机译:Perlecan域1重组蛋白聚糖增强BMP-2活性和成骨作用

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摘要

BackgroundMany growth factors, such as bone morphogenetic protein (BMP)-2, have been shown to interact with polymers of sulfated disacharrides known as heparan sulfate (HS) glycosaminoglycans (GAGs), which are found on matrix and cell-surface proteoglycans throughout the body. HS GAGs, and some more highly sulfated forms of chondroitin sulfate (CS), regulate cell function by serving as co-factors, or co-receptors, in GF interactions with their receptors, and HS or CS GAGs have been shown to be necessary for inducing signaling and GF activity, even in the osteogenic lineage. Unlike recombinant proteins, however, HS and CS GAGs are quite heterogenous due, in large part, to post-translational addition, then removal, of sulfate groups to various positions along the GAG polymer. We have, therefore, investigated whether it would be feasible to deliver a DNA pro-drug to generate a soluble HS/CS proteoglycan in situ that would augment the activity of growth-factors, including BMP-2, in vivo.
机译:背景研究表明,许多生长因子(例如骨形态发生蛋白(BMP)-2)与被称为硫酸乙酰肝素(HS)糖胺聚糖(GAG)的硫酸盐歧化酶的聚合物相互作用,这些分子在人体的基质和细胞表面蛋白聚糖中均被发现。 HS GAG和一些硫酸化程度更高的硫酸软骨素(CS)通过在与受体的GF相互作用中充当辅因子或辅受体来调节细胞功能,并且已证明HS或CS GAG对于甚至在成骨谱系中也能诱导信号传导和GF活性。然而,与重组蛋白不同,HS和CS GAG的异质性很大,这在很大程度上是由于翻译后添加硫酸盐基团然后沿GAG聚合物的各个位置去除了硫酸盐基团。因此,我们研究了递送DNA前药在原位产生可溶的HS / CS蛋白聚糖是否可行,该蛋白会增强体内包括BMP-2在内的生长因子的活性。

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