EMBRYONIC BONE FORMATION DURING ALUMINUM TOXICITY

铝中毒期间的胚胎骨形成

• 批准号: 3438197
• 负责人: CONRAD FIRLING
• 金额: $ 8.98万
• 依托单位: UNIVERSITY OF MINNESOTA DULUTH
• 依托单位国家: 美国
• 财政年份: 1990
• 资助国家: 美国
• 起止时间: 1990-04-09 至 1994-04-08
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3438197
• 关键词: alkaline phosphatase; aluminum; atomic absorption spectrometry; blood chemistry; bone development; bone development disorder; bone metabolism; calcium; cell differentiation; cell population study; chick embryo; collagen; enzyme mechanism; extracellular matrix; femur; histochemistry /cytochemistry; histology; metal poisoning; nonmammalian vertebrate embryology; normal ossification; osteoblasts; osteogenesis; parathyroid hormones; phosphorus; proteoglycan; radioimmunoassay; radionuclides; spectrometry; statistics /biometry

The long term objective of this project is to gain information concerning the mechanism(s) by which aluminum causes bone pathology. Elevated levels of aluminum in bone have been implicated in the etiology of several osteodystrophies in individuals with chronic renal failure. The characteristic features of these pathologies include defective bone mineralization, normal or increased osteoid, and reduced bone cell number and activity. Aluminum intoxication during embryonic and fetal development has been associated with gross skeletal abnormalities. There is no information on the cellular mechanisms by which aluminum perturbs bone formation during early development. This research will utilize long bone development in the chick embryo as an experimental model. The specific research will provide information on the relationship between aluminum toxicity and (a) osteoprogenitor cell proliferation and differentiation (Specific Aim 1), (b) osteoblast activity in extracellular matrix production (Specific Aim 2) and mineralization (Specific Aim 3), and (c) circulating levels of systemic factors (PTH, calcium, phosphorus), and local factors (bone Gla protein, alkaline phosphatase activity) regarded as regulators and/or indicators of bone formation and metabolism (Specific Aim 4). The specific aims will be accomplished by histological and histochemical investigation, histomorphometric analysis, and biochemical measurements of the long bone of chick embryos exposed to chronic aluminum intoxication. In addition to information on the possible mode of action of aluminum toxicity on bone development, the use of aluminum as a relatively specific blocker of bone formation should allow a better understanding of the regulatory processes may also be important in other diseases of the skeletal system.

该项目的长期目标是获得有关 铝引起骨病理的机制。 水平升高 骨中铝的含量与几种 慢性肾衰竭患者的骨营养不良。 的 这些病变的特征包括有缺陷的骨 矿化、正常或增加的类骨质和减少的骨细胞数量 和活动。 胚胎和胎儿发育过程中的铝中毒 与骨骼异常有关 没有 铝干扰骨的细胞机制的信息 在早期发展中形成。 这项研究将利用长骨 作为实验模型的鸡胚发育。 具体 研究将提供有关铝之间关系的信息， 毒性和（a）骨祖细胞增殖和分化 （具体目的1），（B）细胞外基质中的成骨细胞活性 生产（具体目标2）和矿化（具体目标3），以及（c） 全身因子（PTH、钙、磷）的循环水平，以及 局部因素（骨Gla蛋白、碱性磷酸酶活性）被视为 骨形成和代谢的调节剂和/或指示剂（特定目的 4）。 具体目标将通过组织学和 组织化学研究、组织形态计量学分析和生物化学 慢性铝暴露鸡胚长骨的测量 中毒 除了提供关于可能的作用方式的信息外， 铝对骨骼发育的毒性，使用铝作为相对 骨形成的特定阻滞剂应该能够更好地理解 调节过程在其他疾病中也可能是重要的， 骨骼系统