BONE-BONE MARROW INTERACTION

骨与骨髓的相互作用

• 批准号: 3176257
• 负责人: MINAKO Y LEE
• 金额: $ 13.2万
• 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 1992-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3176257
• 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.

本研究计划的长期目标是增加 我们对生理相互关系的了解 造血组织和骨组织，寻找可能的作用 造血细胞对骨转换的调节。 使用动物 del 与高钙血症相关的肿瘤诱导的粒细胞增多症， 并分离出更多衍生的体液因子， 将探讨增生性骨箭中的骨吸收。 在下一个资助期内，骨细胞的研究 刺激和骨吸收体液剂证明 CE 乳腺癌细胞克隆将被研究 与粒细胞生长因子的分子关系 通过使用分子探针从肿瘤中精心制作 造血生长因子特异性抗血清，常规 生化纯化程序和基因分析 表达。 精确分析破骨细胞的新方法 将在体外建立来自骨髓的祖细胞， 表征并用于骨吸收活性的测定。 分离的CE肿瘤源性骨调节的体内功能 或粒细胞生成因子将在体内测试其能力 护理小鼠骨石症。 CE 乳腺癌的作用- 衍生因子以及各种纯化的造血生长因子 骨吸收过程中的因素将通过体外探索 使用分离的骨形成细胞、骨髓进行培养实验 基质细胞、骨髓单核细胞和骨颗粒以及 生长因子介导的骨吸收机制 解剖的。 这些研究将揭示许多尚未解答的基本问题 关于造血生长因子缺陷的问题 骨髓和骨转换的生理学；以及了解 与不明原因高钙血症相关的病理生理学 某些肿瘤。