Role of Cbfa1 Phosphorylation in Bone Metabolism

Cbfa1 磷酸化在骨代谢中的作用

• 批准号: 6622280
• 负责人: Guozhi Xiao
• 金额: $ 7.49万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-01-01 至 2004-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6622280
• 关键词: animal tissue; autoradiography; biomechanics; bone metabolism; bone regeneration; cell differentiation; cell population study; cell proliferation; cytokine; developmental genetics; dogs; gel electrophoresis; gene expression; genetic regulation; immunoprecipitation; in situ hybridization; intermolecular interaction; laboratory rat; mitogen activated protein kinase; osteogenesis; phosphorylation; polymerase chain reaction; posttranslational modifications; protein structure function; transcription factor; western blottings

DESCRIPTION: (provided by applicant) Cbfal is essential for the differentiation of osteoblasts from mesenchymal precursors, during early stages of bone formation. It is also required for maintenance of differentiated osteoblasts. Extracellular matrix synthesis stimulates Cbfal activity through a pathway involving MAP kinase and Cbfal phosphorylation. MAP kinase-dependent Cbfal phosphorylation may play an important role in the regulation of bone formation and regeneration. Our long-term goal is to understand how Cbfal phosphorylation is regulated by signals known to affect osteogenesis and the relationship between Cbfal phosphorylation and bone formation and regeneration. Our previous study led to the development of the following two hypotheses that will be in this project: 1. Bone growth factors and cytokines including BMP-2, TGF-bl, IGF-1, FG F-1 and 2, PDGF-BB, and IL-6 regulate MAP pathways and Cbfal phosphorylation. Cbfal phosphorylation is essential for activation of transcription and regulation of osteoblastic proliferation, differentiation and bone formation. 2. Mechanical loading stimulates MAP kinase pathways and Cbfal phosphorylation, thus, increase osteoblastic activity and bone formation. These hypotheses will be addressed through achievement of the following specific aims: 1. Determine the effects including BMP-2, TGF-bl, IGF-1, FGF-1 and 2, PDGF-BB, and IL-6 on MAPK and Cbfal phosphorylation levels; relate these changes to osteoblastic proliferation and differentiation. 2. Determine the effects of mechanical loading on MAPK and Cbfal phosphorylation levels as well as on osteoblastic proliferation and differentiation. These studies will provide useful fundamental new knowledge regarding the molecular mechanism of bone formation and regeneration by bone growth factors and cytokines as well as by mechanical loading.

描述：(由申请人提供)Cbfal是差异化所必需的 间充质前体细胞在骨早期的成骨细胞 队形。它也是维持分化的成骨细胞所必需的。 细胞外基质合成通过一条途径刺激Cbfal活性 涉及MAP激酶和Cbfal的磷酸化。MAP激酶依赖的Cbfal 磷酸化可能在骨形成的调节中发挥重要作用 和再生。我们的长期目标是了解Cbfal的磷酸化 受已知的影响成骨的信号及其关系的调节 Cbfal磷酸化与骨形成和再生之间的关系。我们以前的 研究导致了以下两个假设的发展，这两个假设将在 本项目： 1.骨生长因子和细胞因子，包括骨形态发生蛋白-2、转化生长因子-1、胰岛素样生长因子-1、纤维蛋白原F-1和 2、PDGF-BB和IL-6调节MAP通路和Cbfal的磷酸化。Cbfal 磷酸化是转录激活和调控的关键。 成骨细胞的增殖、分化和骨形成。2.机械设备 负荷刺激MAP激酶通路和Cbfal磷酸化，因此， 增强成骨活性和骨形成。 这些假设将通过实现以下几点来解决 具体目标：1.测定骨形态发生蛋白-2、转化生长因子-β1、胰岛素样生长因子-1、成纤维细胞生长因子-1的影响 和2、PDGF-BB和IL-6对MAPK和Cbfal磷酸化水平的影响； 成骨细胞增殖和分化的变化。2.确定 机械负荷对MAPK和Cbfal磷酸化水平的影响 AS对成骨细胞增殖和分化的影响。 这些研究将提供有用的基础性新知识 骨生长因子促进骨形成和再生的分子机制 和细胞因子，以及通过机械加载。