Maleski M P, Knudson C B
Department of Biochemistry, Rush Medical College, Rush-Presbyterian-St. Luke's Medical Center, Chicago, Illinois 60612-3864, USA.
Exp Cell Res. 1996 May 25;225(1):55-66. doi: 10.1006/excr.1996.0156.
Cell condensations are the initial structures in the formation of proper cartilage and skeletal patterning in the developing vertebrate limb. Chondrogenic differentiation is dependent upon the cell-cell and/or cell-matrix interactions which take place during the condensation process. Coincident with the onset of condensation is the expression by limb mesenchyme of specific cell surface binding sites for the extracellular matrix macromolecule hyaluronan. The association of hyaluronan with the cell surface can influence the behavior of cells, especially cell aggregation. In this study the possible involvement of hyaluronan as an extracellular linker molecule in the cell-cell adhesion event during mesenchymal condensation was investigated in the avian limb model. Hyaluronan hexasaccharides were used to prevent the multivalent interactions that occur between native hyaluronan macromolecules and the cell surface. Our studies show that hyaluronan is required for early adhesive cell-cell interactions of limb bud mesenchyme and that perturbations of hyaluronan-cell interactions with hyaluronan hexasaccharides result in a delay in the formation of condensations as well as a delay in chondrogenic differentiation of mesenchymal cells in micromass cultures.
细胞凝聚是发育中的脊椎动物肢体中形成正常软骨和骨骼模式的初始结构。软骨形成分化取决于在凝聚过程中发生的细胞间和/或细胞与基质的相互作用。与凝聚开始同时发生的是肢体间充质细胞对细胞外基质大分子透明质酸的特定细胞表面结合位点的表达。透明质酸与细胞表面的结合会影响细胞行为，尤其是细胞聚集。在本研究中，在鸟类肢体模型中研究了透明质酸作为细胞外连接分子在间充质凝聚过程中细胞间黏附事件中的可能作用。使用透明质酸六糖来阻止天然透明质酸大分子与细胞表面之间发生的多价相互作用。我们的研究表明，透明质酸是肢体芽间充质早期黏附性细胞间相互作用所必需的，并且透明质酸六糖对透明质酸 - 细胞相互作用的干扰会导致凝聚形成延迟以及微团培养中间充质细胞软骨形成分化延迟。
