BIOLOGY OF CELL-CELL COMMUNICATION IN BONE

骨骼重塑的特征是一系列“耦合”的序列 成骨细胞及其前体细胞与分化细胞的相互作用 成骨细胞和骨吸收破骨细胞，即 由复杂的旁分泌-内分泌-自分泌相互作用控制 局部和全身骨营养因子。这个多学科项目 将细胞和分子生物学的技术和概念应用于 分析对骨营养因子的生物反应的细胞模式， 并追求细胞-细胞和细胞基质相互作用在 这些反应的转导。将探讨的具体主题包括： 1)成骨细胞产生的因子的分离和鉴定 诱导前体细胞分化为成骨吸收细胞 诱导前体细胞分化为吸收细胞 破骨细胞；2)破骨细胞来源的细胞因子和 其他调节成骨细胞分化的分泌产物；3) 研究破骨细胞所必需的信号转导机制 骨形成的调控；4)研究骨的分子控制 吸收，在分化细胞中强调H+ATPase的放大 破骨前单核-巨噬细胞系的蛋白水解酶(S) 破骨细胞分化过程中的激活与非基因组信号 对1，25(OH)2D3的转导反应；以及5)分析表达和 细胞基质(整合素)和其他细胞黏附分子的合成， 以及成骨细胞调控之间的关系 成骨因子诱导分化及其对细胞的影响 通过这些整合素和细胞黏附分子进行通讯。一个 被指定为“细胞生物学核心”的专业资源中心将 协助开发、准备和维护新的 细胞系和免疫组织化学技术，以及集中的 Cdna探针库。

Skeletal remodeling is characterized by a series of "coupled" sequential interactions between osteoblastic and precursors and the differentiated bone forming osteoblast and bone resorbing osteoclast, which is controlled by a complex paracrine-endocrine-autocrine interplay between local and systemic osteotrophic factors. This multidisciplinary program will apply the techniques and concepts of cell and molecular biology to analyze cellular modes of biological responses to osteotrophic factors, and to pursue the role of cell-cell and cell matrix interaction in the transduction of these responses. Specific themes to be explored will be: 1) isolation and identification of factors produced by osteoblasts which induce the differentiation of precursor cells into resorptive osteoblasts which induce the differentiation of precursor cells into resorptive osteoclasts; 2) characterization of osteoclast-derived cytokines and other secretory products that modulate osteoblast differentiation; 3) examine signal transduction mechanisms which are essential for osteoclast regulation of osteogenesis; 4) examine the molecular control of bone resorption, emphasizing H+ ATPase amplification in differentiating cells of the pre-osteoclastic monocyte-macrophage lineage, protease(s) activation during osteoclast differentiation, and non-genomic signal transductive responses to 1,25(OH)2D3; and 5) analyze the expression and synthesis of cell matrix (integrins) and other cell adhesion molecules, as well as the relationship between regulation of osteoblast differentiation by osteotropic factors and their effect on cell communication via these integrins and cell adhesion molecules. A specialized resource center designated the "Cell Biology Core" will provide assistance in the development, preparation and maintenance of new cell lines and immunohistochemical techniques, and a centralized repository for cDNA probe.