BIOLOGY OF CELL/CELL COMMUNICATION IN BONE

骨细胞/细胞通讯的生物学

• 批准号: 6029936
• 负责人: Roberto Civitelli
• 金额: $ 122.92万
• 依托单位: BARNES-JEWISH HOSPITAL
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-08-10 至 2002-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6029936
• 关键词: cell cell interaction; osteoblasts; osteoclasts; osteogenesis

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.

骨骼重塑的特点是细胞间通讯 破骨细胞和成骨细胞前体之间的网络等 分化的骨形成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 蛋白质和局部和局部之间的旁分泌-内分泌-自分泌相互作用 全身性骨营养因子。这个多学科研究计划 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型， 并探究细胞-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 提议：（i）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 细胞因子和生长因子对其的影响；并确定关键的 介导相互作用的信号转导途径 整合素、基质蛋白和成骨细胞功能； （二）分析角色 破骨细胞激活中的金属蛋白酶和基质裂解 确定激活的结构要求的目标， 表征激活所需的破骨细胞受体，以及 确定破骨细胞中液泡 H+ATP 酶极化的作用 和成骨细胞活性反应； (iii) 分析整合素的作用 当它们参与产生时对机械应变的响应 人类成骨细胞的合成代谢信号和细胞骨架变化； (四) 至 定义破骨细胞衍生趋化因子的概况并分析激素、 成骨细胞发育的细胞因子和基质依赖性调节， 迁移和功能； (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的函数 活动。被指定为“细胞生物学”的专业资源中心 核心实验室”将提供实验方面的帮助和咨询 设计、适当细胞培养物的制备、免疫化学、 细胞因子ELISA、原位杂交技术支持 分析和 cDNA 探针的集中存储库。