BONE CELL DIFFERENTIATION VIA CELL ADHESION

骨形成是由成骨细胞介导的多步骤过程， 各种循环内分泌因子除了局部非 控制成骨细胞生长的激素物质， 通过旁分泌和自分泌模式分化。 一切都很好- 确定激素和非激素对骨生成的影响是 通过从外部传递到内部的信号来调节 细胞对配体结合的反应， 信使和这些基因的最终转录， 协调成骨细胞的生长和分化。 生物 信号也可以从细胞内部传输， 细胞粘附分子以及细胞之间的结合亲和力， 缝隙连接 事实上，早期的观察表明， 细胞可以粘附到多种细胞外基质基质（ECM）上， 现在已经扩展到揭示各种整合素是 成骨细胞表达，整合素-ECM相互作用是一个重要因素。 在生物信号的转导中， 调节成骨细胞对营养因子的反应。 此外，Cell 在成骨细胞中也发现了粘附分子 在胚胎发育过程中。 因此，我们计划继续假设 细胞-细胞和细胞-基质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表达。 实现 为此，我们将分析细胞基质的表达和合成， 在人类和啮齿动物成骨细胞系中， 如在正常的原代培养物中。 我们的实验都是为了 分析细胞粘附分子调节的机制 利用骨髓基质干细胞向成骨细胞分化 群体和表型表达的特异性生物标记 成骨细胞的分化。 促钙激素和 其他对CAMs表达和功能的成骨因子将 以及监管之间的相关性， 成骨细胞分化的骨营养因子及其作用 细胞间接触 这些研究结果将提供重要的 深入了解这些监管程序， 成骨细胞分化成骨形成（矿化）细胞，和 从而促进这些属性的潜在开发， 体外刺激成骨细胞发育和功能或 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.