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Unintended targeting of Dmp1-Cre reveals a critical role for Bmpr1a signaling in the gastrointestinal mesenchyme of adult mice

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Bone Research 2017年第1期5卷 41-48页

作者： joohyun lim Joseph Burclaff Guangxu He Jason C Mills Fanxin Long Department of Orthopaedic Surgery Washington University School of MedicineSt.LouisMOUSA Division of Gastroenterology Departments of Medicine and Pathology and ImmunologyWashington University School of MedicineSt.LouisMOUSA Department of Orthopedics The Second Xiangya HospitalCentral South UniversityHunan 410011China Department of Developmental Biology Washington University School of MedicineSt.LouisMOUSA

Cre/loxP technology has been widely used to study cell type-specific functions of genes. Proper interpretation of such data critically depends on a clear understanding of the tissue specificity of Cre expression. The Dmpl- Cre mouse, expressing Cre from a 14-kb DNA fragment of the mouse Dmpl gene, has become a common tool for studying gene function in osteocytes, but the presumed cell specificity is yet to be fully established. By using the Ai9 reporter line that expresses a red fluorescent protein upon Cre recombination, we find that in 2-month-old mice, Dmpl-Cre targets not only osteocytes within the bone matrix but also osteoblasts on the bone surface and preosteoblasts at the metaphyseal chondro-osseous junction. In the bone marrow, Cre activity is evident in certain stromal cells adjacent to the blood vessels, but not in adipocytes. Outside the skeleton, Dmpl-Cre marks not only the skeletal muscle fibers, certain cells in the cerebellum and the hindbrain but also gastric and intestinal mesenchymal cells that express Pdgfra. Confirming the utility of Dmpl-Cre in the gastrointestinal mesenchyme, deletion of Bmprla with Dmpl-Cre causes numerous large polyps along the gastrointestinal tract, consistent with prior work involving inhibition of BMP signaling. Thus, caution needs to be exercised when using Dmpl-Cre because it targets not only the osteoblast lineage at an earlier stage than previously appreciated, but also a number of non-skeletal cell types.

关键词： gene cell bone Unintended targeting of Dmp1-Cre reveals a critical role for Bmpr1a signaling in the gastrointestinal mesenchyme of adult mice Figure

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Differential involvement of Wnt signaling in Bmp regulation of cancellous versus periosteal bone growth

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Bone Research 2017年第3期5卷 217-227页

作者： Guangxu He Yu Shi joohyun lim Teresita Bellido Jiangdong Ni Fanxin Long Department of Orthopedics The Second Xiangya Hospital Central South University Department of Orthopaedic Surgery Washington University School of Medicine Department of Molecular and Human Genetics Baylor College of Medicine Department of Anatomy and Cell Biology Indiana University School of Medicine Department of Developmental Biology Washington University School of Medicine

Bone morphogenetic proteins （Bmp） are well-known to induce bone formation following chondrogenesis, but the direct role of Bmp signaling in the osteoblast lineage is not completely understood. We have recently shown that deletion of the receptor Bmprla in the osteoblast lineage with Dmpl-Cre reduces osteoblast activity in general but stimulates proliferation of preosteoblasts specifically in the cancellous bone region, resulting in diminished periosteal bone growth juxtaposed with excessive cancellous bone formation. Because expression of sclerostin （SOST）, a secreted Wnt antagonist, is notably reduced in the Bmprla- deficient osteocytes, we have genetically tested the hypothesis that increased Wnt signaling might mediate the increase in cancellous bone formation in response to Bmprla deletion. Forced expression of human SOST from a Dmpl promoter fragment partially rescues preosteoblast hyperproliferation and cancellous bone overgrowth in the Bmprla mutant mice, demonstrating functional interaction between Bmp and Wnt signaling in the cancellous bone compat^a-tent. To test whether increased Wnt signaling can compensate for the defect in periosteal growth caused by Bmprla deletion, we have generated compound mutants harboring a hyperactive mutation （A214V） in the Wnt receptor Lrp5. However, the mutant Lrp5 does not restore periosteal bone growth in the Bmprla-deficient mice. Thus, Bmp signaling restricts cancellous bone accrual partly through induction of SOST that limits preosteoblast proliferation, but promotes periosteal bone growth apparently independently of Wnt activation.

关键词： Figure Differential involvement of Wnt signaling in Bmp regulation of cancellous versus periosteal bone growth Wnt

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Towards maximized utilization of iridium for the acidic oxygen evolution reaction

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Nano Research 2019年第9期12卷 2275-2280页

作者： Marc Ledendecker Simon Geiger Katharina Hengge joohyun lim Serhiy Cherevko Andrea M. Mingers Daniel Gohl Guilherme V. Fortunato Daniel Jalalpoor Ferdi Schuth Christina Scheu Karl J. J. Mayrhofer Department of Interface Chemistry and Surface Engineering Nanoanalytics and Interfaces Max-Planck-Institut fur Eisenforschung GmbH40237 DusseldorfGermany Department of Heterogeneous Catalysis Max-Planck-Institut fur KohlenforschungKaiser- Wilhelm-Platz 145470 Mulheim an der RuhrGermany Helmholtz-Institute Erlangen-Nurnbergfar Renewable Energy (IEK-11) Forschungszentrum Jillich91058 ErlangenGermany Department of Chemical and Biological Engineering Friedrich-Alexander- Universitat Erlangen -Nurnberg91058 ErlangenGermany Institute of Chemistry Universidade Federal de Mato Grosso do SulAv. Senador Filin to Muller1555Campo GrandeMS 79074-460Brazil

The reduction in noble metal content for efficient oxygen evolution catalysis is a crucial aspect towards the large scale commercialisation of polymer electrolyte membrane *** catalytic stability and activity are inversely related,long service lifetime still demands large amounts of low-abundant and expensive *** this manuscript we elaborate on the concept of maximizing the utilisation of iridium for the oxygen evolution *** combining different tin oxide based support materials with liquid atomic layer deposition of iridium oxide,new possibilities are opened up to grow thin layers of iridium oxide with tuneable noble metal ***-situ,time-and potential-resolved dissolution experiments reveal how the stability of the substrate and the catalyst layer thickness directly affect the activity and stability of deposited iridium *** on our results,we elaborate on strategies how to obtain stable and active catalysts with maximized iridium utilisation for the oxygen evolution reaction and demonstrate how the activity and durability can be tailored *** results highlight the potential of utilizing thin noble metal films with earth abundant *** for future catalytic applications in the energy sector.

关键词： oxygen evolution reaction liquid atomic layer depositi on catalysis iridium core-shell nano particles

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