EPIDERMAL GROWTH FACTOR EFFECTS ON OSTEOBLASTIC CELLS

表皮生长因子受体是一种跨膜糖蛋白。 具有酪氨酸激酶活性。在大多数细胞类型中， 研究表明，EGF可产生促有丝分裂反应。EGF已被证明可以 在体内和体外与成骨细胞结合。在骨器官培养中 系统，EGF产生更多的骨吸收，增加PGE2 分泌减少，胶原合成减少。EGF也被发现 增加骨肉瘤细胞系和原代细胞中PGE2的产量 从鸡头盖骨中培养细胞。在我们的实验室里，我们已经证明 EGF促进G292细胞系和原代细胞的增殖 从新生大鼠颅骨分离培养成骨细胞。其作用机制 酪氨酸激酶受体通过哪些途径在骨细胞中产生反应 还没有被描述出来。我们已经用一种 多种第二信使抑制物，以及百日咳毒素 使G(I)蛋白失活，以剖析一连串的事件 这导致了G292和原代培养的EGF有丝分裂反应 成骨细胞。来自我们实验室的数据表明，各种秒的作用 G292和G292在EGF增殖反应中的信使不同 原代培养细胞。我们的目标是进一步探索 两种细胞类型之间的差异。此外，我们有兴趣 EGF在成骨细胞电生理中的作用。 有证据表明，在A431人表皮样癌细胞中， 以酪氨酸激酶依赖的方式，可以调节钙离子通道。我们 正在计划研究EGF在调节脑内离子通道中的作用 成骨细胞。继续调查是我们研究的目的 与成骨细胞对EGF的反应有关的事件。 总而言之，这些研究将增进我们对骨骼的了解 酪氨酸激酶受体激活引起的骨吸收 成骨细胞。 关键词：成骨细胞，表皮生长因子，骨吸收 有丝分裂

The epidermal growth factor (EGF) receptor is transmembrane glycoprotein with tyrosine-kinase activity. In most of the cell types which have been studied, EGF produces a mitogenic response. EGF has been shown to bind to osteoblastic cells in vivo and vitro. In bone organ culture systems, EGF produces increased bone resorption, increased PGE2 production and decreased collagen synthesis. EGF was also found to increase PGE2 production in osteosarcoma cell lines as well as primary culture cells from chick calvaria. In our laboratory we have shown that EGF increases cell proliferation in the G292 cell line and in primary culture osteoblasts isolated from neonatal rat calvaria. The mechanisms by which tyrosine-kinase receptors produce their response in bone cells has not been characterized. We have done proliferation studies using a variety of second messenger inhibitors, as well as pertussis toxin which inactivates G(i) proteins, in order to dissect the cascade of events which results in the EGF mitogenic response in G292 and primary culture osteoblasts. Data from our lab suggest that the role of various second messengers in the EGF proliferative response are different for G292 and primary culture cells. It is our goal to further explore the differences between the two cell types. In addition we are interested in the role of EGF on the electrophysiology of osteoblastic cells. There is evidence in the A431 human epidermoid carcinoma cell that EGF, in a tyrosine-kinase dependent fashion, can regulate Ca2+ channels. We are planning to look at the role of EGF in regulation of ion channels in osteoblasts. It is the aim of our studies to continue the investigation of events involved in the osteoblastic response to EGF. In summary, these studies will enhance our understanding of bone resorption resulting from activation of a tyrosine-kinase receptor in osteoblastic cells. Key Words: osteoblasts, epidermal growth factor, bone resorption, mitogenesis