Loss of the Hematopoietic Stem Cell Factor GATA2 in the Osteogenic Lineage Impairs Trabecularization and Mechanical Strength of Bone [Research Article]
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)
Published 2018
The American Society for Microbiology (ASM)
Published 2018
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: |
_version_ | 1836398950044663808 |
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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 |