BONE AND BONE MARROW INTERACTION

这项研究的长期目标是增加 我们对生理相互关系的了解 造血组织和骨组织，寻求可能的作用， 造血细胞调节骨转换。 使用动物 与高钙血症相关的肿瘤诱导的粒细胞增多症的缺失， 分离更多的体液因子， 将探讨增生骨中的骨吸收。 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从 将研究CE乳腺癌细胞克隆的 与粒细胞生成生长因子的分子关系还 通过使用分子探针， 常规造血生长因子特异性抗血清 生化纯化程序和基因分析 表情 一种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肿瘤源性骨调节剂的体内功能 或粒细胞生成因子将在体内测试其能力， 护理小鼠的石骨症。 CE乳腺癌的作用- 衍生因子以及各种纯化的造血生长因子 通过体外实验，探讨骨吸收过程中的影响因素， 使用分离的骨形成细胞、骨髓 基质细胞、骨髓单核细胞和骨颗粒， 生长因子介导的骨吸收的机制将是 解剖。 这些研究揭示了许多未解的基本问题， 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 不明原因高钙血症的病理生理学 某些肿瘤

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.