BONE AND BONE MARROW INTERACTION

这项研究提案的长期目标是增加 我们对生理上的相互关系的认识 造血组织和骨组织，寻求可能的作用 造血细胞在骨转换调节中的作用。用一只动物 与高钙血症相关的肿瘤诱导的粒细胞增多症， 并分离出更多派生的体液因子，其机制 将探讨骨吸收在增生性骨箭中的作用。 在下一次资助期间，骨细胞的研究 刺激性和骨吸收体液制剂从 将对CE乳腺癌细胞克隆进行研究 与粒细胞生长因子的分子关系也 通过使用分子探针从肿瘤中阐述，以及 常规造血生长因子特异性抗血清 生化提纯程序及基因分析 表情。一种精确分析破骨细胞的新方法 体外培养的骨髓祖细胞将被建立， 表征并用于骨吸收活性的测定。 分离的CE瘤源骨调节作用的体内研究 或粒细胞因子将在体内进行测试，以确定其是否具有 治疗小鼠骨化症。CE乳腺癌的作用-- 衍生因子以及各种纯化的造血生长 骨吸收过程中的因素将通过体外实验进行探索 利用分离的骨形成细胞、骨髓进行培养实验 基质细胞、骨髓单个核细胞和骨颗粒 生长因子介导的骨吸收机制将是 被解剖了。这些研究揭示了许多未回答的基本问题 关于造血生长因子缺陷的几个问题 骨髓生理学和骨转换；以及理解 不明原因高钙血症的病理生理学研究 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.