BIOLOGY OF CELL/CELL COMMUNICATION IN BONE

骨骼重塑的特征是细胞间的沟通 破骨细胞和成骨细胞前体之间的网络以及更多 分化的成骨细胞和骨吸收破骨细胞， 所有这些都是由与骨基质的复杂相互作用控制的 蛋白质与局部和局部的旁分泌-内分泌-自分泌相互作用 全身性骨营养因子。这项多学科研究计划 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型， 并探讨细胞-细胞和细胞-基质相互作用在 这些反应的转导。为了实现这些目标，我们 建议：(一)分析整合素-基质蛋白之间的关系 成骨细胞生长和分化的相互作用及其机制 细胞因子和生长因子在其上的作用；并确定关键 介导细胞间相互作用的信号转导通路 整合素、基质蛋白与成骨细胞功能；(Ii)分析其作用 破骨细胞活化中金属蛋白酶和基质裂解的研究 确定激活的结构要求的目标是， 表征激活所需的破骨细胞受体，以及 空泡H+-ATPase极化在破骨细胞中的作用 和成骨细胞活性反应；(Iii)分析整合素在 对机械应变的反应，因为它们参与了 人成骨细胞的合成代谢信号和细胞骨架变化； 定义破骨细胞衍生的趋化因子的图谱并分析荷尔蒙， 细胞因子和基质依赖的成骨细胞发育调控 迁移和功能；以及(V)鉴定和表征趋化因子 成骨细胞上的受体作为成骨细胞分化和分化的功能 活动。被命名为“细胞生物学”的专业资源中心 “核心实验室”将在实验中提供帮助和咨询 设计、适当细胞培养的制备、免疫化学、 细胞因子的ELISA，原位杂交的技术支持 分析，以及一个集中的cdna探针储存库。

Skeletal remodeling is characterized by an intercellular communicating network between osteoclastic and osteoblastic precursors and more differentiated bone forming osteoblast and the bone resorbing osteoclast, all of which is controlled by a complex interaction with bone matrix proteins and a paracrine-endocrine-autocrine interplay between local and systemic osteotrophic factors. This multidisciplinary research program will apply the techniques and concepts of cell and molecular biology to analyze cellular models of biological responses to osteotrophic factors, and to pursue the role of cell-cell and cell-matrix interactions in the transduction of these responses. In order to achieve these goals we propose to: (i) analyze the relationships between integrins-matrix protein interactions to the growth and differentiation of osteoblasts and the effects of cytokines and growth factors thereon; and to identify pivotal signal transduction pathways which mediate the interactions between integrins, matrix proteins and osteoblast function; (ii) analyze the role of metalloproteinases and matrix cleavage in osteoclast activation with the goals of identifying the structural requirements for activation, characterizing the osteoclast receptors necessary for activation, and determining the role of vacuolar H+ATPase polarization in the osteoclastic and osteoblastic activity response; (iii) analyze the role of integrins in response to mechanical strain as they participate in the generation of anabolic signals and cytoskeletal changes in the human osteoblast; (iv) to define a profile of osteoclast-derived chemokines and to analyze hormonal, cytokine and matrix-dependent modulation of osteoblast development, migration and function; and (v) to identify and characterize the chemokine receptors on osteoblasts as a function of osteoblast differentiation and activity. A specialized resource center designated as the "Cell Biology Core Laboratory" will provide assistance and consultation in experimental designs, preparation of appropriate cell cultures, immunochemistry,, ELISAs for cytokines, technical support for in situ hybridization analyses, and a centralized repository for cDNA probes.