Loss of the Hematopoietic Stem Cell Factor GATA2 in the Osteogenic Lineage Impairs Trabecularization and Mechanical Strength of Bone

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dc.contributor.author Tolkachov, Alexander
dc.contributor.author Fischer, Cornelius
dc.contributor.author Ambrosi, Thomas H.
dc.contributor.author Bothe, Melissa
dc.contributor.author Han, Chung-Ting
dc.contributor.author Muenzner, Matthias
dc.contributor.author Mathia, Susanne
dc.contributor.author Salminen, Marjo
dc.contributor.author Seifert, Georg
dc.contributor.author Thiele, Mario
dc.contributor.author Duda, Georg N.
dc.contributor.author Meijsing, Sebastiaan H.
dc.contributor.author Sauer, Sascha
dc.contributor.author Schulz, Tim J.
dc.contributor.author Schupp, Michael
dc.date.accessioned 2018-08-22T08:53:01Z
dc.date.available 2018-08-22T08:53:01Z
dc.date.issued 2018-06
dc.identifier.citation Tolkachov , A , Fischer , C , Ambrosi , T H , Bothe , M , Han , C-T , Muenzner , M , Mathia , S , Salminen , M , Seifert , G , Thiele , M , Duda , G N , Meijsing , S H , Sauer , S , Schulz , T J & Schupp , M 2018 , ' Loss of the Hematopoietic Stem Cell Factor GATA2 in the Osteogenic Lineage Impairs Trabecularization and Mechanical Strength of Bone ' , Molecular and Cellular Biology , vol. 38 , no. 12 , UNSP e00599-17 . https://doi.org/10.1128/MCB.00599-17
dc.identifier.other PURE: 115209541
dc.identifier.other PURE UUID: d1795899-900f-4d3f-9b32-b6057036dbaf
dc.identifier.other WOS: 000433419600008
dc.identifier.other Scopus: 85047795063
dc.identifier.other ORCID: /0000-0003-0696-6845/work/47804940
dc.identifier.uri http://hdl.handle.net/10138/238981
dc.description.abstract The transcription factor GATA2 is required for expansion and differentiation of hematopoietic stem cells (HSCs). In mesenchymal stem cells (MSCs), GATA2 blocks adipogenesis, but its biological relevance and underlying genomic events are unknown. We report a dual function of GATA2 in bone homeostasis. GATA2 in MSCs binds near genes involved in skeletal system development and colocalizes with motifs for FOX and HOX transcription factors, known regulators of skeletal development. Ectopic GATA2 blocks osteoblastogenesis by interfering with SMAD1/5/8 activation. MSC-specific deletion of GATA2 in mice increases the numbers and differentiation capacity of bone-derived precursors, resulting in elevated bone formation. Surprisingly, MSC-specific GATA2 deficiency impairs the trabecularization and mechanical strength of bone, involving reduced MSC expression of the osteoclast inhibitor osteoprotegerin and increased osteoclast numbers. Thus, GATA2 affects bone turnover via MSC-autonomous and indirect effects. By regulating bone trabecularization, GATA2 expression in the osteogenic lineage may contribute to the anatomical and cellular microenvironment of the HSC niche required for hematopoiesis. en
dc.format.extent 16
dc.language.iso eng
dc.relation.ispartof Molecular and Cellular Biology
dc.rights unspecified
dc.rights.uri info:eu-repo/semantics/openAccess
dc.subject GATA2
dc.subject bone
dc.subject cell differentiation
dc.subject mesenchymal stem cell
dc.subject osteoblast
dc.subject trabecularization
dc.subject ACTIVATED RECEPTOR-GAMMA
dc.subject TRANSCRIPTION FACTOR GATA-2
dc.subject LARGE GENE LISTS
dc.subject ADIPOCYTE DIFFERENTIATION
dc.subject REGULATES DIFFERENTIATION
dc.subject OSTEOCLAST DEVELOPMENT
dc.subject CONTROL ADIPOGENESIS
dc.subject BROWN ADIPOCYTES
dc.subject CRE RECOMBINASE
dc.subject DEFICIENT MICE
dc.subject 1182 Biochemistry, cell and molecular biology
dc.title Loss of the Hematopoietic Stem Cell Factor GATA2 in the Osteogenic Lineage Impairs Trabecularization and Mechanical Strength of Bone en
dc.type Article
dc.contributor.organization Doctoral Programme in Clinical Veterinary Medicine
dc.contributor.organization Marjo Salminen / Principal Investigator
dc.contributor.organization Veterinary Biochemistry and Cell Biology
dc.contributor.organization Veterinary Biosciences
dc.description.reviewstatus Peer reviewed
dc.relation.doi https://doi.org/10.1128/MCB.00599-17
dc.relation.issn 0270-7306
dc.rights.accesslevel openAccess
dc.type.version acceptedVersion

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