BONE AND BONE MARROW INTERACTION

骨和骨髓的相互作用

• 批准号: 2082054
• 负责人: MINAKO Y LEE
• 金额: $ 16.48万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 1984
• 资助国家: 美国
• 起止时间: 1984-06-15 至 1997-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2082054
• 关键词: antiserum; bioassay; bone marrow; breast neoplasms; cell bank /registry; cell population study; chromatography; clone cells; colony stimulating factor; cytokine; disease /disorder model; granulocyte; hematopoietic tissue; histochemistry /cytochemistry; hypercalcemia; interleukin 3; laboratory mouse; leukocyte activation /transformation; leukocytosis; leukopoiesis; leukopoietic factor; messenger RNA; molecular oncology; newborn animals; oncoproteins; osteoclasts; osteopetrosis; physiologic bone resorption; radiotracer; transforming growth factors

The long term objective of this research proposal is to increase our knowledge in physiological interrelationships between hemopoietic tissue and bone tissue, seeking a possible role of hemopoietic cells in regulation of bone turnover. Using an animal del of tumor-induced granulocytosis associated with hypercalcemia, and isolating the more derived humoral factors, the mechanisms of bone resorption in hyperplastic bone arrow will be explored. During the next grant period, the investigation of bone cell stimulating and bone resorbing humoral agents demonstrated from the CE mammary carcinoma cell clones will be investigated for their molecular relationships to granulopoieticc growth factors also elaborated from the tumor, by the use of molecular probes, well as specific antisera of hemopoietic growth factors, conventional biochemical purification procedures and analysis of gene expression. A new method to precisely analyses osteoclast progenitors from the bone marrow in vitro will be established, characterized and utilized for assays of bone resorbing activities. The in vivo function of isolated CE tumor derived bone modulating or granulopoietic factor will be tested in vivo for its ability to care osteopetrosis in mice. The role of the CE mammary carcinoma- derived factor as well as various purified hemopoietic growth factors in bone resorbing process will be explored by in vitro culture experiments using isolated bone forming cells, marrow stromal cells, marrow mononuclear cells and bone particles and the mechanism of growth factor mediated bone resorotion will be dissected. These studies are to disclose many unanswered basic questions about the defect of hemopoietic growth factors on physiology of bone marrow and bone turnover; well as to understand pathophysiology of unexplained hypercalcemia associated with certain tumors.

这项研究计划的长期目标是增加