BONE CELL DIFFERENTIATION VIA CELL ADHESION

通过细胞粘附进行骨细胞分化

• 批准号: 6235700
• 负责人: LOUIS V AVIOLI
• 金额: $ 22.75万
• 依托单位: BARNES-JEWISH HOSPITAL
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-04-01 至 1998-08-09
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6235700
• 关键词: biomarker; cell adhesion; cell adhesion molecules; cell cell interaction; cell differentiation; cell growth regulation; extracellular matrix; gap junctions; gene expression; human tissue; immunofluorescence technique; immunoprecipitation; in situ hybridization; integrins; laboratory rat; northern blottings; nucleic acid probes; osteoblasts; osteogenesis; polymerase chain reaction; protein biosynthesis; tissue /cell culture; western blottings

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.

骨形成是一个由成骨细胞和骨细胞介导的多步骤过程 除了局部非内分泌因素外，还有多种循环内分泌因素 激素物质的作用是控制成骨细胞的生长和 通过旁分泌和自分泌模式进行分化。 已经很好了—— 确定激素和非激素对成骨的影响 由从外部传输到内部的信号介导 细胞对配体结合的反应，刺激第二 信使和这些基因的最终转录至关重要 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，调制 细胞粘附分子以及细胞之间的结合亲和力 间隙连接。 事实上，早期的观察表明，骨骼 细胞可以粘附到多种细胞外基质基质（ECM） 现在已被扩展以揭示多种整合素 由成骨细胞表达，整合素-ECM 相互作用是 生物信号转导中所需的、即时的事件 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粘附分子（CAM） 在胚胎发生过程中。 因此，我们计划追求假设 细胞-细胞和细胞-基质接触对于转导至关重要 那些对于启动和调节至关重要的生物事件 成骨细胞特征的有序表达。 达到 这个目标我们将分析细胞基质的表达和合成 人类和啮齿动物成骨细胞系中的（整合素）和 CAM 与正常的原代培养物一样。 我们的实验都是为了 解析细胞粘附分子调节机制 利用骨祖细胞骨髓基质细胞分化成骨细胞 表型表达的群体和特定生物标记 成骨细胞分化。 促钙激素和促钙激素的作用 其他成骨因子对 CAM 表达和功能的影响 进行评估，以及监管之间的相关性 骨营养因子对成骨细胞的分化及其影响 细胞与细胞的接触。 这些研究的结果应该提供重要的 深入了解对于这些监管流程至关重要 成骨细胞分化为骨形成（矿化）细胞，以及 从而促进这些财产的潜在开发 刺激成骨细胞发育和功能体外或 体内成骨。