EXPRESSION AND REGULATION OF GAP JUNCTIONS IN BONE CELLS

拟议中的研究试图定义 缝隙连接蛋白在骨骼中的表达和功能受调控 细胞。参与骨形成和重塑的细胞必须能够 共同发挥作用以有效地维持骨骼，他们做到了 对局部和荷尔蒙刺激的反应。主要的方式之一就是 细胞之间通过缝隙连接进行交流。差距 连接蛋白是由六聚体组成的完整的膜蛋白，称为 在相邻细胞质之间形成水通道的连接蛋白 细胞。这些结构允许电池的电和化学耦合 在许多肿瘤的细胞生长、肿瘤发生和发育过程中起重要作用。 不同的细胞。以前已经在骨骼中发现了缝隙连接 在电子显微镜下观察细胞。对这项提议的初步研究已经 显示人和大鼠成骨细胞和细胞系表达三种 缝隙连接蛋白家族的不同成员。 此外，成骨细胞的沟通能力也不同。 通过缝隙连接，不同的连接蛋白似乎发挥作用 成骨细胞在细胞间通讯中的不同作用。因为很多人 连接蛋白已经被克隆和测序，现在有可能 在正常不表达的细胞中表达单个缝隙连接蛋白 表达它们，以便研究它们的功能。中概述的研究 这项提案将定义不同的缝隙连接蛋白如何 有助于成骨细胞的细胞间通讯，以及如何 这些蛋白的表达和功能受局部和 全身性介质，如细胞因子、激素和信号介质 影响骨细胞功能的转导。因此，这些研究可能 阐明骨细胞功能调节的重要机制， 并提出了影响骨骼重塑的新方法。

The proposed studies seek to define the molecular mechanisms by which the expression and function of gap junction proteins is controlled in bone cells. The cells involved in bone formation and remodeling must be able to function in concert to effectively maintain bone, and they do so in response to local and hormonal stimuli. One of the major ways in which cells communicate with each other is through gap junctions. Gap junctions are composed of hexamers of integral membrane proteins called connexins which form aqueous channels between the cytoplasm of adjacent cells. These structures allow electrical and chemical coupling of cells and are important in cell growth, oncogenesis, and development in many different cells. Gap junctions have been identified previously in bone cells by electron microscopy. Preliminary studies for this proposal have shown that human and rat osteoblastic cells and cell lines express three different members of the connexin family of gap junction proteins. Furthermore, osteoblastic cells differed in their ability to communicate through gap junctions, and the different connexins appear to play different roles in cell-cell communication in osteoblasts. Because many of the connexins have been cloned and sequenced, it is now possible to express individual gap junction proteins in cells that do not normally express them in order to study their function. The studies outlined in this proposal will define how the different gap junction proteins contribute to cell-cell communication in osteoblastic cells, and how the expression and function of these proteins are controlled by local and systemic mediators such as cytokines, hormones, and mediators of signal transduction that affect bone cell function. These studies may thereby elucidate important mechanisms by which bone cell function is regulated, and suggest novel ways in which bone remodeling can be influenced.