LEAD EFFECTS ON THE EPIPHYSEAL GROWTH PLATE

铅对骨骺生长板的影响

• 批准号: 2770757
• 负责人: DAVID G HICKS
• 金额: $ 11.38万
• 依托单位: UNIVERSITY OF ROCHESTER
• 依托单位国家: 美国
• 财政年份: 1995
• 资助国家: 美国
• 起止时间: 1995-09-01 至 2000-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2770757
• 关键词: alkaline phosphatase; atomic absorption spectrometry; autocrine; biological signal transduction; cartilage development; cartilage metabolism; cell differentiation; chickens; chondrocytes; epiphysis; glycoprotein biosynthesis; immunocytochemistry; in situ hybridization; laboratory rat; lead poisoning; northern blottings; nucleic acid probes; paracrine; phenotype; protein kinase C; proteoglycan; radioimmunoassay; scintillation spectrometry; second messengers; tissue /cell culture

Lead toxicity is a major public health problem in the United States. The results of the second National Health and Nutrition Examination Survey demonstrated a highly significant inverse correlation of blood lead level with growth, suggesting a biologic effect of the metal ion on developmental aspects of the epiphyseal growth plate. It is unclear, however, whether the effect of lead is mediated through a systemic pathway or a specific effect on the growth plate chondrocytes. This proposal seeks to explore the relationship between direct lead effects on cartilage metabolism and the detrimental results of lead on skeletal growth. The research goals are to examine and fully characterize lead's effects on chondrocyte phenotype in vitro. These studies will utilize an avian model of growth plate differentiation which has been well characterized in our laboratory. Specifically the experiments will define the effects of lead on proliferation, alkaline phosphatase expression, matrix proteins and proteoglycan synthesis in cell culture. Subsequent studies will focus on identification of the specific mechanisms of lead effects on growth plate chondrocytes. These studies will explore the role of lead on the autocrine and paracrine regulation of chondrocyte differentiation by determining the ability of the cells to respond to, or synthesize, these regulator molecules in the presence of the ion. In the final phase of these studies we will examine the in vivo effects of lead on growth plate structure and function in a whole animal model as well as in a new cell pellet culture model that retains features of the intact tissue. A detailed cellular and molecular characterization of the effects of lead on chondrocyte phenotype that is focused on mechanisms of the toxicity will significantly enhance our understanding of the adverse effects of this agent on the developing skeleton.

铅毒性是美国的主要公共卫生问题。 第二次国家健康和营养考试的结果 调查表明血液具有非常显着的反相关性 铅水平随生长的水平，表明金属离子对生物学作用 骨生长板的发育方面。目前尚不清楚， 但是，铅的效果是否是通过全身性介导的 途径或对生长板软骨细胞的特定影响。这 提案旨在探索直接铅效应之间的关系 关于软骨代谢和铅铅的有害结果 生长。 研究目标是检查并充分表征Lead的效果 在体外软骨细胞表型上。这些研究将利用禽类 生长板分化的模型，该模型已经表征了 在我们的实验室。具体而言，实验将定义效果 增殖，碱性磷酸酶表达，基质的铅 细胞培养中的蛋白质和蛋白聚糖合成。随后的研究 将专注于识别铅效应的特定机制 在生长板软骨细胞上。这些研究将探讨 铅对软骨细胞的自分泌和旁分泌调节 通过确定细胞响应的能力来分化， 或合成，这些调节剂分子在离子存在下。在 这些研究的最后阶段，我们将研究的体内影响 引导整个动物模型中的生长板结构和功能 以及在保留的新细胞颗粒培养模型中 完整的组织。 详细的细胞和分子表征的作用 铅上的软骨细胞表型，重点是 毒性将大大增强我们对不利的理解 该试剂对发育中的骨骼的影响。