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

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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

Title: Loss of the Hematopoietic Stem Cell Factor GATA2 in the Osteogenic Lineage Impairs Trabecularization and Mechanical Strength of Bone
Author: Tolkachov, Alexander; Fischer, Cornelius; Ambrosi, Thomas H.; Bothe, Melissa; Han, Chung-Ting; Muenzner, Matthias; Mathia, Susanne; Salminen, Marjo; Seifert, Georg; Thiele, Mario; Duda, Georg N.; Meijsing, Sebastiaan H.; Sauer, Sascha; Schulz, Tim J.; Schupp, Michael
Contributor: University of Helsinki, Doctoral Programme in Clinical Veterinary Medicine
Date: 2018-06
Language: eng
Number of pages: 16
Belongs to series: Molecular and Cellular Biology
ISSN: 0270-7306
URI: http://hdl.handle.net/10138/238981
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.
Subject: GATA2
bone
cell differentiation
mesenchymal stem cell
osteoblast
trabecularization
ACTIVATED RECEPTOR-GAMMA
TRANSCRIPTION FACTOR GATA-2
LARGE GENE LISTS
ADIPOCYTE DIFFERENTIATION
REGULATES DIFFERENTIATION
OSTEOCLAST DEVELOPMENT
CONTROL ADIPOGENESIS
BROWN ADIPOCYTES
CRE RECOMBINASE
DEFICIENT MICE
1182 Biochemistry, cell and molecular biology
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