DIFFERENTIAL VOLUME CONTROL BY HYPERTROPHIC CHONDROCYTES

在出生后的生长过程中，长骨末端软骨生长板的软骨细胞通过分化级联进行，该分化级联由作为增殖软骨细胞的干细胞克隆扩增启动，并在软骨细胞肥大期间以终末分化结束。 在快速生长的哺乳动物生长板中，肥大期间的软骨细胞增大已被证明是理解骨骼长度生长的细胞控制机制的重要变量。 在本提案中，将通过以下方式研究生长板软骨细胞的体积调节：1）测量体积增加期间积累的特定细胞内渗透调节物质，并分析每种物质对体积增加的定量贡献;和2）检查特定转运蛋白活性的分布体积增加期间生长板不同区域，首先关注Na+/K+泵。 该提案概述了实验，以启动系统的探索，发现在生长板软骨细胞的多个体积控制的调节机制，并涉及到一个基本问题的理解，在生长板生物学-软骨细胞通过细胞膨胀控制差异的生长速度-通过检查离子和非离子体积控制的多个元素的相互作用的结果。

During postnatal growth, chondrocytes of the cartilaginous growth plates at the end of long bones proceed through a differentiation cascade initiated by stem cell clonal expansion as proliferative chondrocytes and ending with terminal differentiation during chondrocytic hypertrophy. In rapidly growing mammalian growth plates, chondrocytic enlargement during hypertrophy has been demonstrated to be the significant variable for understanding the cellular control mechanisms by which bones grow in length. In this proposal, volume regulation by growth plate chondrocytes will be investigated by: 1) measuring specific intracellular osmolytes that accumulate during volume increase, and analyzing the quantitative contribution of each to volume increase; and 2) examining the distribution of activity of specific transporters during volume increase in different zones of the growth plate, focusing first on the Na+/K+ pump. This proposal outlines experiments to initiate a systematic exploration of the multiple volume control regulatory mechanisms found in growth plate chondrocytes, and relates the results to an understanding of a fundamental question in growth plate biology-- chondrocytic control over differential growth rates through cellular swelling-by examining the interplay of multiple elements of both ionic and non-ionic volume control.