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Loss of the hematopoietic stem cell factor GATA2 in the osteogenic lineage impairs trabecularization and mechanical strength of bone

Item Type:Article
Title:Loss of the hematopoietic stem cell factor GATA2 in the osteogenic lineage impairs trabecularization and mechanical strength of bone
Creators Name:Tolkachov, A. and Fischer, C. and Ambrosi, T.H. and Bothe, M. and Han, C.T. and Muenzner, M. and Mathia, S. and Salminen, M. and Seifert, G. and Thiele, M. and Duda, G.N. and Meijsing, S.H. and Sauer, S. and Schulz, T.J. and Schupp, M.
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 co-localizes 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 numbers and differentiation capacity of bone-derived precursors, resulting in elevated bone formation. Surprisingly, MSC-specific GATA2 deficiency impairs 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.
Keywords:GATA2, Bone, Cell Differentiation, Mesenchymal Stem Cell, Osteoblast, Trabecularization, Animals, Mice
Source:Molecular and Cellular Biology
ISSN:0270-7306
Publisher:American Society for Microbiology
Volume:38
Number:12
Page Range:e00599-17
Date:June 2018
Official Publication:https://doi.org/10.1128/MCB.00599-17
External Fulltext:View full text on PubMed Central
PubMed:View item in PubMed

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