BIOLOGY OF CELL-CELL COMMUNICATION IN BONE

骨骼重塑的特点是一系列“耦合”的顺序 成骨细胞和前体细胞之间的相互作用以及分化的 骨形成成骨细胞和骨吸收破骨细胞， 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。 这一多学科计划 将应用细胞和分子生物学的技术和概念， 分析对骨营养因子的生物反应的细胞模式， 并探讨细胞与细胞和细胞基质相互作用在 这些反应的传导。 将探讨的具体主题包括： 1)分离和鉴定成骨细胞产生的因子， 诱导前体细胞分化为吸收性成骨细胞 其诱导前体细胞分化为吸收性的 破骨细胞; 2）破骨细胞衍生的细胞因子的表征， 调节成骨细胞分化的其他分泌产物; 3） 研究破骨细胞所必需的信号转导机制 骨生成的调节; 4）检查骨的分子控制 吸收，强调分化细胞中H+ ATP酶的扩增 前骨坏死单核细胞-巨噬细胞谱系的蛋白酶 破骨细胞分化过程中的激活，以及非基因组信号 对1，25（OH）2D 3的转导应答;和5）分析表达， 细胞基质（整联蛋白）和其它细胞粘附分子的合成， 以及成骨细胞的调节 成骨因子诱导的骨细胞分化及其对细胞的作用 通过这些整合素和细胞粘附分子进行信息交流。 一 专门的资源中心指定的“细胞生物学核心”将 协助发展、筹备和维持新的 细胞系和免疫组织化学技术，以及一个集中的 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.