EMBRYONIC BONE FORMATION DURING ALUMINUM TOXICITY

这个项目的长期目标是获得关于 铝引起骨骼病理的机制(S)。升高的水平 骨骼中的铝与几种疾病的病因有关 慢性肾功能衰竭患者的骨营养不良。这个 这些病理的特征包括骨缺陷。 矿化，类骨质正常或增多，骨细胞数量减少 和活动。胚胎和胎儿发育过程中的铝中毒 与严重的骨骼异常有关。没有 铝干扰骨骼的细胞机制的研究进展 在发育早期形成的。这项研究将利用长骨 以鸡胚胎发育为实验模型。具体的 研究将提供关于铝和铝之间关系的信息 毒性和(A)骨祖细胞的增殖和分化 (特定目标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)，和(C) 循环中的系统因子水平(甲状旁腺素、钙、磷)，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(特定目标 4)。具体目标将通过组织学和 组织化学调查、组织形态计量学分析和生化 慢性铝暴露对雏鸡胚胎长骨的影响 喝醉了。除了关于可能的行动模式的信息之外 铝对骨骼发育有毒性，使用铝作为一种相对 特定的骨形成阻滞剂应该能更好地理解 调控过程在其他疾病中也可能很重要。 骨骼系统。

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.