DOWN-REGUL OF BONE MORPHOG PROTEIN-11 BY ITS PROPEPTIDE DURING EMBRYONIC DEV

胚胎发育过程中骨形态蛋白11前肽的下调

• 批准号: 8360325
• 负责人: Jinzeng Yang
• 金额: $ 4.06万
• 依托单位: UNIVERSITY OF HAWAII AT MANOA
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-07-01 至 2012-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8360325
• 关键词: Amino Acid Sequence; Animal Model; Animals; Applications Grants; Biogenesis; Biological Assay; Bone Morphogenetic Proteins; Bromodeoxyuridine; Cell Culture Techniques; Cell Proliferation; Centers of Research Excellence; Cervical spine; Cessation of life; Congenital Abnormality; Data; Depressed mood; Development; Embryo; Embryonic Development; Funding; Gene Expression; Grant; Human; Institutes; Knockout Mice; Knowledge; Label; Life; Mesenchymal Stem Cells; Molecular; Musculoskeletal; National Center for Research Resources; Newborn Infant; Osteoblasts; Osteogenesis; Pilot Projects; Preparation; Principal Investigator; Proteins; Publishing; Regulation; Research; Research Infrastructure; Research Methodology; Resources; Role; Source; Staging; Transgenic Mice; Transgenic Organisms; United States National Institutes of Health; Western Blotting; base; bone; cost; design; fetal; growth-differentiation factor 8; in vivo; mouse model; muscle form; myogenesis; myostatin; novel strategies; osteogenic; prevent; promoter; skeletal; skeletal abnormality; spine bone structure; thoracic vertebra bone structure

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Bone morphogenetic protein 11 (BMP-11 or GDF-11) has 90% identity in amino acid sequences with myostatin or GDF-8. BMP-11 knockout mice caused dramatic transformation of vertebrae and death of newborns. Also, it may act like myostatin to regulate muscle mass. However, the specific roles of BMP-11 in regulation of skeletal formation during embryonic and fetal stages have not been well defined. Based on our previous evidence that transgenic expression of myostatin propeptide significantly depressed myostatin function and increased muscle mass, we generated transgenic mice that over-express BMP-11 propeptide under the control of an osteoblast-specific promoter. Live animals were born with transformed cervical vertebra to a thoracic vertebra. This BMP-11 propetide mouse model offers an important animal model for studying the role of BMP-11 in musculoskeletal formation and development. This pilot project is designed to characterize skeletal formation and myogenesis of BMP-11 propeptide transgenic mice during the embryonic and fetal periods, and further to investigate the role of BMP-11 and its propeptide in the regulation of differentiation of mesenchymal stem cells to osteogenic and chondrogenic lineage. Research methods will incorporate transgenic mice and cell culture with in vivo BrdU labeling for cell proliferation assay, gene expression analysis by qRT-PCR and Western blotting. Results from this project are expected to reveal molecular and cellular mechanisms that control bone formation during embryo development, which is important for understanding skeletal abnormalities and birth defects. The new knowledge of these regulatory mechanisms may help to develop novel strategies for preventing human birth defects. The immediate, direct benefit of this project for us is to obtain and publish the preliminary data for the preparation of a NIH grant application.

该副本是利用资源的众多研究子项目之一 由NIH/NCRR资助的中心赠款提供。对该子弹的主要支持 而且，副投影的主要研究员可能是其他来源提供的 包括其他NIH来源。 列出的总费用可能 代表subproject使用的中心基础架构的估计量， NCRR赠款不直接向子弹或副本人员提供的直接资金。 骨形态发生蛋白11（BMP-11或GDF-11）在氨基酸序列中具有90％的身份，与肌生抑素或GDF-8具有90％的身份。 BMP-11敲除小鼠引起了椎骨和新生儿死亡的巨大转变。同样，调节肌肉质量可能像肌抑制素一样。然而，BMP-11在胚胎和胎儿阶段调节骨骼形成中的特定作用尚未得到很好的定义。基于我们先前的证据，表明肌抑制素前肽的转基因表达显着抑制肌抑制素功能并增加肌肉质量，我们产生了转基因小鼠，该小鼠在控制成骨细胞特异性启动子的控制下过表达BMP-11丙肽。活动物天生有颈椎变成胸椎。该BMP-11 Propetide小鼠模型提供了一个重要的动物模型，用于研究BMP-11在肌肉骨骼形成和发育中的作用。该试点项目旨在表征胚胎和胎儿时期BMP-11丙肽转基因小鼠的骨骼形成和肌发生，并进一步研究BMP-11及其在调节间质干细胞分化对骨质和软骨发育层的调节中的作用。研究方法将与体内BRDU标记进行细胞增殖测定法，QRT-PCR和Western blotting的基因表达分析结合到体内BRDU标记和细胞培养。该项目的结果有望揭示在胚胎发育过程中控制骨形成的分子和细胞机制，这对于理解骨骼异常和出生缺陷很重要。这些监管机制的新知识可能有助于制定预防人类出生缺陷的新型策略。该项目对我们的直接好处是获取并发布用于准备NIH赠款申请的初步数据。