BONE CELL DIFFERENTIATION VIA CELL ADHESION

骨形成是一个多步骤的过程，由成骨细胞和 循环内分泌因子的变化除局部非 控制成骨细胞生长的激素物质和 旁分泌和自分泌模式的分化。一切都很顺利- 证实荷尔蒙和非荷尔蒙对成骨的影响是 由从外部传递到内部的信号进行传递 细胞对配体结合的反应，这刺激了第二 信使和那些必不可少的基因的最终转录 协调成骨细胞的生长和分化。生物学 信号也可以从单元内部传输，以调制 细胞黏附分子的结合亲和力以及细胞间通过 缝隙连接。事实上，早期的观察证明了这块骨头 细胞可以附着在多种细胞外基质(ECM)上。 现已扩展到揭示各种整合素是 在成骨细胞中表达，整合素-ECM相互作用是 在生物信号的传递过程中所需要的、立即发生的事件 调节成骨细胞对营养因子的反应。此外，细胞 成骨细胞中也发现了黏附分子(Cam)。 在胚胎发育过程中。因此，我们计划继续这一假设。 细胞-细胞和细胞-基质的接触对于转导是必不可少的 这些生物事件对于启动和调节 成骨细胞特征的有序顺序表达。要实现 为此，我们将分析细胞基质的表达和合成 (整合素)和CaM在人和啮齿动物成骨细胞系中的表达 就像在正常的初级培养中一样。我们的实验都是为了 分析细胞黏附分子的调节机制 骨祖细胞向成骨细胞分化的实验研究 表型表达的群体和特异性生物标记 成骨细胞分化。促降钙素激素和 其他促骨因子对CAMWill表达和功能的影响 被评估，以及监管之间的相关性 骨营养因子诱导成骨细胞分化及其对成骨细胞生长的影响 细胞-细胞接触。这些研究的结果应该提供重要的 深入了解对以下各项至关重要的监管流程 成骨细胞分化为骨形成(矿化)细胞，以及 从而促进了对这些财产的潜在开发 体外对成骨细胞发育和功能的促进作用 体内成骨。

Bone formation is a multistep process mediated by the osteoblast and a variety of circulating endocrine factors in addition to local non- hormonal substances which function to control osteoblast growth and differentiation via paracrine and autocrine modes. It has been well- established that hormonal and non-hormonal effects on osteogenesis are mediated by signals which are transmitted from the outside to the inside of cells in the response to ligand binding, which stimulates second messengers and the ultimate transcription of those genes essential to coordinate the growth and differentiation of the osteoblast. Biological signals can also be transmitted from the inside of cells modulating the binding affinity of cell adhesion molecules as well as between cells via gap junctions. In fact early observations which demonstrated that bone cells can adhere to a variety of extracellular matrix substrates (ECM) have now been extended to reveal that a variety of integrins are expressed by osteoblasts, and that the integrin-ECM interaction is a required, immediate event in the transduction of biological signals which condition the osteoblast response to trophic factors. Moreover, cell adhesions molecules (CAMs) have also been identified in osteoblasts during embryogenesis. Consequently, we plan to pursue the hypothesis that cell-cell and cell-matrix contact are essential for the transduction of those biological events which are essential to initiate and modulate the orderly sequential expression of osteoblastic traits. To achieve this goal we will analyze the expression and synthesis of cell matrix (integrins) and CAMs in human and rodent osteoblastic cell lines as well as in normal primary cultures. Our experiments are all designed to analyze the mechanism by which cell adhesion molecules regulate osteoblast differentiation utilizing osteoprogenitor marrow stromal cell populations and specific biological markers of the phenotypic expression of osteoblast differentiation. The effects of calcitropic hormones and other osteotropic factors on the expression and function of the CAMs will be evaluated, as well as the correlation between the regulation of osteoblast differentiation by osteotrophic factors and their effect on cell-cell contact. Results of these studies should provide important insight into those regulatory processes which are essential for osteoblast differentiation into bone forming (mineralizing) cells, and thus facilitate potential exploitation of these properties for the stimulation of osteoblastic development and function in vitro or osteogenesis in vivo.