Lemons Michele L, Sandy John D, Anderson Douglas K, Howland Dena R
Department of Pharmacology and Therapeutics and Center for Research in Pediatric Orthopedics, Shriners Hospital, University of South Florida, Tampa, FL 33612, USA.
Exp Neurol. 2003 Dec;184(2):981-90. doi: 10.1016/S0014-4886(03)00383-2.
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.
聚集蛋白聚糖是一种硫酸软骨素（CS）/硫酸角质素（KS）取代的蛋白聚糖（PG），在软骨中含量丰富，在哺乳动物胚胎、成年和成年损伤的中枢神经系统（CNS）中也有存在。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成年损伤轴突在体内的抑制作用，我们开发了一个模型来独立测试完整的聚集蛋白聚糖和CS缺失的聚集蛋白聚糖核心糖蛋白。将急性大鼠脊髓半切空洞用促进生长的基质基质胶填充，并将切断的背根小束放入该基质中。这创建了一个轴突易于生长的检测方法。将该基线检测中的向内生长程度与加载完整聚集蛋白聚糖或聚集蛋白聚糖纯化核心糖蛋白的基质胶中的向内生长程度进行比较。我们的结果表明，完整的聚集蛋白聚糖和等效浓度的核心糖蛋白成分在该模型系统中均显著抑制轴突生长。这些结果证实聚集蛋白聚糖可在体内抑制成年轴突生长，并表明聚集蛋白聚糖的抑制作用可能至少部分由在没有大部分CS链的情况下位于核心糖蛋白上的结构介导。
