Sorreli J M, Carrino D A, Caplan A I
Skeletal Research Center and Biology Department, Case Western Reserve University, Cleveland, OH 44106, USA.
Int J Dev Neurosci. 1996 Jun;14(3):233-48. doi: 10.1016/0736-5748(96)00010-x.
Chondroitin sulfate proteoglycans, cell surface and extracellular matrix molecules in both neural and non-neural tissues, are highly regulated during normal development. Entire proteoglycan molecules may be either up-regulated or down-regulated, or only the chondroitin sulfate glycosaminoglycan portions of these molecules may be modified. Subtle changes in the chemistries of chondroitin sulfate chains can now be identified through the use of a panel of anti-chondroitin sulfate monoclonal antibodies. Each of these antibodies recognizes specific chemical structures which are non-randomly dispersed along the lengths of chondroitin sulfate chains. The location of individual epitopes within defined domains in these chains is demonstrated through controlled treatments of aggrecan with chondroitinase ABC, whereby portions of these chains are removed from the non-reducing terminal ends and where the remainder of the chains remains covalently attached to the core protein. In these situations, some epitopes, such as those recognized by antibodies CS-56 and 6C3, can be removed without loss of other epitopes, such as that recognized by antibody 4C3. The independent expression of individual epitopes is demonstrated by immunocytochemical analyses of developing skin appendages in embryonic chicks and fetal humans. These are sites where highly patterned morphogenetic movements result from epithelial-mesenchymal interactions. In both chicks and humans, some epitopes are constitutively expressed while others are strictly regulated in the mesenchymal portions of the developing skin appendages. These data strongly suggest that chondroitin sulfate proteoglycans, including their chondroitin sulfate chains, have important roles in regulating these epithelial mesenchymal interactions. Furthermore, these data underscore the significance of the aforementioned observation that individual epitopes are located in specific domains within chondroitin sulfate chains. The highly organized expression of chondroitin sulfate proteoglycans in the development of the central nervous system strongly argues for a similar role for these molecules in the organs that comprise this system.
硫酸软骨素蛋白聚糖是神经组织和非神经组织中的细胞表面及细胞外基质分子，在正常发育过程中受到高度调控。整个蛋白聚糖分子可能上调或下调，或者这些分子中只有硫酸软骨素糖胺聚糖部分会被修饰。现在可以通过使用一组抗硫酸软骨素单克隆抗体来识别硫酸软骨素链化学性质的细微变化。这些抗体中的每一种都识别特定的化学结构，这些结构沿着硫酸软骨素链的长度非随机分布。通过用硫酸软骨素酶ABC对聚集蛋白聚糖进行可控处理，证明了这些链中特定结构域内各个表位的位置，由此这些链的部分从非还原末端被去除，而其余部分仍与核心蛋白共价连接。在这些情况下，一些表位，如被抗体CS-56和6C3识别的表位，可以被去除而不损失其他表位，如被抗体4C3识别的表位。通过对胚胎鸡和胎儿人类发育中的皮肤附属器进行免疫细胞化学分析，证明了各个表位的独立表达。这些部位是上皮-间充质相互作用导致高度模式化形态发生运动的地方。在鸡和人类中，一些表位在发育中的皮肤附属器的间充质部分组成性表达，而其他表位则受到严格调控。这些数据有力地表明，硫酸软骨素蛋白聚糖，包括其硫酸软骨素链，在调节这些上皮-间充质相互作用中具有重要作用。此外，这些数据强调了上述观察结果的重要性，即各个表位位于硫酸软骨素链内的特定结构域中。硫酸软骨素蛋白聚糖在中枢神经系统发育中的高度有序表达有力地证明了这些分子在构成该系统的器官中具有类似的作用。
