Intact aggrecan and chondroitin sulfate-depleted aggrecan core glycoprotein inhibit axon growth in the adult rat spinal cord
Intact aggrecan and chondroitin sulfate-depleted aggrecan core glycoprotein inhibit axon growth in the adult rat spinal cord
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DOI：
10.1016/s0014-4886(03)00383-2
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发表时间：
2003-12-01
影响因子：
5.3
通讯作者：
Howland, DR
中科院分区：
文献类型：
--
作者：
Lemons, ML;Sandy, JD;Howland, DR
聚集蛋白聚糖是软骨中富含的硫酸软骨素（CS）/硫酸角质素（KS）取代的蛋白聚糖（PG），其也存在于哺乳动物胚胎、成人和受损的成人中枢神经系统（CNS）中。尽管其在中枢神经系统中的作用尚不清楚，但细胞培养研究表明，当用CS取代时，聚集蛋白聚糖会抑制神经突延伸。为了更好地理解聚集蛋白聚糖对体内损伤的成体轴突的抑制作用，我们开发了一种模型来独立地测试完整的聚集蛋白聚糖和CS耗尽的聚集蛋白聚糖核心糖蛋白。急性大鼠脊髓半切腔充满了生长促进基质，基质胶，切断背根被放置到这个矩阵。这创造了一个轴突容易生长的试验。将该基线测定中的向内生长程度与负载有完整聚集蛋白聚糖或纯化的聚集蛋白聚糖核心糖蛋白的Matrigel中的向内生长进行比较。我们的研究结果表明，完整的聚集蛋白聚糖和等效浓度的核心糖蛋白组分显着抑制轴突生长在这个模型系统。这些结果证实，聚集蛋白聚糖可以抑制成人轴突在体内的生长，并表明聚集蛋白聚糖的抑制作用可能介导，至少部分地，由位于核心糖蛋白的结构在没有大部分的CS链。(C)2003年爱思唯尔公司All rights reserved.
Aggrecan is a chondroitin sulfate (CS)/keratan sulfate (KS)-substituted proteoglycan (PG) abundant in cartilage which is also present within the mammalian embryonic, adult, and injured adult central nervous system (CNS). Although its role within the CNS is not clear, cell culture studies show that when substituted with CS, aggrecan inhibits neurite extension. To better understand the inhibitory effect of aggrecan on injured adult axons in vivo, we developed a model to independently test intact aggrecan and CS-depleted aggrecan core glycoprotein. Acute rat spinal cord hemisection cavities were filled with a growth-promoting matrix, Matrigel, and severed dorsal rootlets were placed into this matrix. This created an assay in which axons readily grew. The extent of ingrowth in this baseline assay was compared to the ingrowth in Matrigel loaded with intact aggrecan or the purified core glycoprotein of aggrecan. Our results show that both intact aggrecan and equivalent concentrations of the core glycoprotein component significantly inhibit axonal growth in this model system. These results confirm that aggrecan can inhibit the growth of adult axons in vivo and suggest that the inhibitory effects of aggrecan may be mediated, at least in part, by structures located on the core glycoprotein in the absence of the bulk of the CS chains. (C) 2003 Elsevier Inc. All rights reserved.