CELL REGULATION OF GROWTH PLATE MATRIX MINERALIZATION

生长板基质矿化的细胞调节

• 批准号: 3079140
• 负责人: Joseph P. Iannotti
• 金额: $ 7.66万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 1984
• 资助国家: 美国
• 起止时间: 1984-07-01 至 1989-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3079140
• 关键词: atomic absorption spectrometry; calcification; calcitonin; cartilage metabolism; cell growth regulation; cell membrane; cholecalciferol; chondrocytes; cytochrome c; extracellular matrix; fluorescent dye /probe; homeostasis; hormone regulation /control mechanism; hypoxia; membrane permeability; mitochondria; normal ossification; oxygen tension; parathyroid hormones; phosphorus metabolism; vitamin metabolism

The original goals of the first three years of this Clinical Investigator Award were: 1) to define the organelles that regulate intracellular calcium homeostasis in chondrocytes from various zones of the growth plate, 2) to study the effects of parathyroid hormone, calcitonin, somatomedins and the vitamin D3 metabolites on intracellular ionized calcium, 3) to study the effect of hypoxia on calcium regulation in the growth plate chondrocyte. During the first two years of funding (1984-1986) I completed the first two of these objectives and obtained additional funding to complete the design and manufacture of specialized equipment of begin the study of the third objective. During the third year of this award (1986-1987), I plan to complete the preliminary study and equipment calibration necessary to study the effect of hypoxia on intracellular calcium homeostasis in the growth plate chondrocyte. During the two years of funding requested in this grant renewal (1987-1989) the first goal will be to complete the study of hypoxia on intracellular calcium transport. During the 1988-1989 funding year, we will use a technique of high voltage electric fields to nondestructively permeabilize the plasma membrane in order to manipulate the intracellular ionized calcium concentration and study the effect of increased (Cai) on matrix vesicle formation and collagen metabolism. During these five year of funding we will accomplish a much more complete understanding of the regulation of intracellular calcium in the growth plate, the effect of the hormonal milieu and microenvironmental hypoxia on intracellular calcium, and the effect on increased intracellular calcium on growth plate chondrocyte metabolism. This data will lead to a better overall understanding of growth plate physiology and specifically define the role of intracellular calcium in growth plate physiology and matrix mineralization. A significant portion of the original proposal has been completed and the preliminary portion of experiments outlined in this proposal are underway. In order to complete this work an additional two years of funding is requested under this Clinical Investigator Award.

本次临床前三年的最初目标 研究者奖是：1）定义了以下细胞器： 调节软骨细胞内钙稳态 生长板的各个区域，2) 研究 甲状旁腺激素、降钙素、生长调节素和维生素 D3 代谢物对细胞内离子钙的影响，3) 研究 缺氧对生长板钙调节的影响 软骨细胞。 在资助的头两年（1984-1986）我 完成了前两个目标并获得 额外资金来完成设计和制造 专门设备开始第三个目标的研究。 在该奖项的第三年（1986-1987），我计划 完成前期研究和设备校准 有必要研究缺氧对细胞内钙的影响 生长板软骨细胞的稳态。 在本次赠款续展中请求资助的两年内 （1987-1989）首要目标是完成缺氧的研究 对细胞内钙转运的影响。 1988-1989年期间资助 今年，我们将使用高压电场技术 非破坏性地透化质膜，以便 操纵细胞内离子钙浓度和 研究增加 (Cai) 对基质囊泡形成的影响 和胶原蛋白代谢。 在这五年的资助期间，我们将完成更多的工作 完全了解细胞内钙的调节 在生长板中，激素环境的影响和 微环境缺氧对细胞内钙的影响 对生长板细胞内钙增加的影响 软骨细胞代谢。 这些数据将带来更好的整体效果 了解生长板生理学并具体定义 细胞内钙在生长板生理学中的作用和 基质矿化。 原提案的很大一部分已经完成 以及本文中概述的实验的初步部分 提案正在进行中。 为了完成这项工作 根据本临床试验要求额外两年的资金 研究员奖。