| Bone vascularization and trabecular bone formation are mediated by PKB alpha/Akt1 in a gene-dosage-dependent manner: in vivo and ex vivo MRI. | |
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MedLine Citation:
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PMID: 20572141 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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PKBalpha/Akt1, a protein kinase, is a major mediator of angiogenic signaling. The purpose of this study was to determine the role of PKB alpha/Akt1 in bone vascularization and development. For that aim, macromolecular dynamic contrast enhanced MRI was applied to examine in vivo vascular changes in long bones of 40-day-old growing PKB alpha/Akt1-deficient, heterozygous, and wild-type mice. Ex vivo microMRI and microCT were applied to monitor the impact of PKB alpha/Akt1 gene dosage on trabecular bone formation during endochondral bone growth. PKB alpha/Akt1-deficient mice and, remarkably, also heterozygous mice showed significantly reduced blood volume fraction in the humerus compared to wild-type mice. Moreover, PKB alpha/Akt1-deficient mice showed a more severe vascular deficiency with reduced permeability. microCT and microMRI of trabeculae revealed impaired bone formation in both PKB alpha/Akt1-deficient and heterozygous mice, whereas cortical bone parameters were only reduced in PKB alpha/Akt1-deficient mice. Reduction of metaphyseal blood vessel invasion, concomitant with aberrant trabeculae and shorter long bones, demonstrates a gene-dose-dependent role for PKB alpha/Akt1 in regulation of overall size and endochondral bone growth. MRI proved to provide high sensitivity for in vivo detection of subtle gene dose effects leading to impaired bone vascularity and for uncovering changes in trabecular bone. |
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Authors:
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Katrien Vandoorne; Jeremy Magland; Vicki Plaks; Amnon Sharir; Elazar Zelzer; Felix Wehrli; Brian A Hemmings; Alon Harmelin; Michal Neeman |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Magnetic resonance in medicine : official journal of the Society of Magnetic Resonance in Medicine / Society of Magnetic Resonance in Medicine Volume: 64 ISSN: 1522-2594 ISO Abbreviation: Magn Reson Med Publication Date: 2010 Jul |
Date Detail:
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Created Date: 2010-06-29 Completed Date: 2010-10-25 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 8505245 Medline TA: Magn Reson Med Country: United States |
Other Details:
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Languages: eng Pagination: 54-64 Citation Subset: IM |
Copyright Information:
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(c) 2010 Wiley-Liss, Inc. |
Affiliation:
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Biological Regulation, The Weizmann Institute of Science, Rehovot, Israel. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Bone Density Gene Dosage* Humerus* / blood supply, growth & development, radiography Immunohistochemistry Magnetic Resonance Imaging Mice Mice, Knockout Proto-Oncogene Proteins c-akt / genetics* |
| Chemical | |
Reg. No./Substance:
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EC 2.7.11.1/Proto-Oncogene Proteins c-akt |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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