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

Publication Date:
2018-05-30
Publisher:
The American Society for Microbiology (ASM)
Print ISSN:
0270-7306
Electronic ISSN:
1098-5549
Topics:
Biology
Medicine
Published by:
http://www.asm.org/
_version_ 1836398950044663808
autor 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.
beschreibung 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.
citation_standardnr 6270912
datenlieferant ipn_articles
feed_id 2374
feed_publisher The American Society for Microbiology (ASM)
feed_publisher_url http://www.asm.org/
insertion_date 2018-05-30
journaleissn 1098-5549
journalissn 0270-7306
publikationsjahr_anzeige 2018
publikationsjahr_facette 2018
publikationsjahr_intervall 7984:2015-2019
publikationsjahr_sort 2018
publisher The American Society for Microbiology (ASM)
quelle Molecular and Cellular Biology
relation http://mcb.asm.org/cgi/content/short/38/12/e00599-17?rss=1
search_space articles
shingle_author_1 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.
shingle_author_2 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.
shingle_author_3 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.
shingle_author_4 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.
shingle_catch_all_1 Loss of the Hematopoietic Stem Cell Factor GATA2 in the Osteogenic Lineage Impairs Trabecularization and Mechanical Strength of Bone [Research Article]
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.
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.
The American Society for Microbiology (ASM)
0270-7306
02707306
1098-5549
10985549
shingle_catch_all_2 Loss of the Hematopoietic Stem Cell Factor GATA2 in the Osteogenic Lineage Impairs Trabecularization and Mechanical Strength of Bone [Research Article]
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.
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.
The American Society for Microbiology (ASM)
0270-7306
02707306
1098-5549
10985549
shingle_catch_all_3 Loss of the Hematopoietic Stem Cell Factor GATA2 in the Osteogenic Lineage Impairs Trabecularization and Mechanical Strength of Bone [Research Article]
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.
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.
The American Society for Microbiology (ASM)
0270-7306
02707306
1098-5549
10985549
shingle_catch_all_4 Loss of the Hematopoietic Stem Cell Factor GATA2 in the Osteogenic Lineage Impairs Trabecularization and Mechanical Strength of Bone [Research Article]
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.
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.
The American Society for Microbiology (ASM)
0270-7306
02707306
1098-5549
10985549
shingle_title_1 Loss of the Hematopoietic Stem Cell Factor GATA2 in the Osteogenic Lineage Impairs Trabecularization and Mechanical Strength of Bone [Research Article]
shingle_title_2 Loss of the Hematopoietic Stem Cell Factor GATA2 in the Osteogenic Lineage Impairs Trabecularization and Mechanical Strength of Bone [Research Article]
shingle_title_3 Loss of the Hematopoietic Stem Cell Factor GATA2 in the Osteogenic Lineage Impairs Trabecularization and Mechanical Strength of Bone [Research Article]
shingle_title_4 Loss of the Hematopoietic Stem Cell Factor GATA2 in the Osteogenic Lineage Impairs Trabecularization and Mechanical Strength of Bone [Research Article]
timestamp 2025-06-30T23:35:13.313Z
titel Loss of the Hematopoietic Stem Cell Factor GATA2 in the Osteogenic Lineage Impairs Trabecularization and Mechanical Strength of Bone [Research Article]
titel_suche Loss of the Hematopoietic Stem Cell Factor GATA2 in the Osteogenic Lineage Impairs Trabecularization and Mechanical Strength of Bone [Research Article]
topic W
WW-YZ
uid ipn_articles_6270912