This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. 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.
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