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Loss of murine Gfi1 causes neutropenia and induces osteoporosis depending on the pathogen load and systemic inflammation

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Loss of murine Gfi1 causes neutropenia and induces osteoporosis depending on the pathogen load and systemic inflammation. / Geissler, Sven; Textor, Martin; Stumpp, Sabine; Seitz, Sebastian; Lekaj, Anja; Brunk, Sabrina; Klaassen, Sabine; Schinke, Thorsten; Klein, Christoph; Mundlos, Stefan; Kornak, Uwe; Kühnisch, Jirko.

In: PLOS ONE, Vol. 13, No. 6, 2018, p. e0198510.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Geissler, S, Textor, M, Stumpp, S, Seitz, S, Lekaj, A, Brunk, S, Klaassen, S, Schinke, T, Klein, C, Mundlos, S, Kornak, U & Kühnisch, J 2018, 'Loss of murine Gfi1 causes neutropenia and induces osteoporosis depending on the pathogen load and systemic inflammation', PLOS ONE, vol. 13, no. 6, pp. e0198510. https://doi.org/10.1371/journal.pone.0198510

APA

Geissler, S., Textor, M., Stumpp, S., Seitz, S., Lekaj, A., Brunk, S., Klaassen, S., Schinke, T., Klein, C., Mundlos, S., Kornak, U., & Kühnisch, J. (2018). Loss of murine Gfi1 causes neutropenia and induces osteoporosis depending on the pathogen load and systemic inflammation. PLOS ONE, 13(6), e0198510. https://doi.org/10.1371/journal.pone.0198510

Vancouver

Geissler S, Textor M, Stumpp S, Seitz S, Lekaj A, Brunk S et al. Loss of murine Gfi1 causes neutropenia and induces osteoporosis depending on the pathogen load and systemic inflammation. PLOS ONE. 2018;13(6):e0198510. https://doi.org/10.1371/journal.pone.0198510

Bibtex

@article{b53605d07eec49089cdbf1f8b72dec00,
title = "Loss of murine Gfi1 causes neutropenia and induces osteoporosis depending on the pathogen load and systemic inflammation",
abstract = "Gfi1 is a key molecule in hematopoietic lineage development and mutations in GFI1 cause severe congenital neutropenia (SCN). Neutropenia is associated with low bone mass, but the underlying mechanisms are poorly characterized. Using Gfi1 knock-out mice (Gfi1-ko/ko) as SCN model, we studied the relationship between neutropenia and bone mass upon different pathogen load conditions. Our analysis reveals that Gfi1-ko/ko mice kept under strict specific pathogen free (SPF) conditions demonstrate normal bone mass and survival. However, Gfi1-ko/ko mice with early (nonSPF) or late (SPF+nonSPF) pathogen exposure develop low bone mass. Gfi1-ko/ko mice demonstrate a striking rise of systemic inflammatory markers according to elevated pathogen exposure and reduced bone mass. Elevated inflammatory cytokines include for instance Il-1b, Il-6, and Tnf-alpha that regulate osteoclast development. We conclude that low bone mass, due to low neutrophil counts, is caused by the degree of systemic inflammation promoting osteoclastogenesis.",
keywords = "Animals, Body Weight, Bone and Bones, Cell Differentiation, Cytokines, DNA-Binding Proteins, Extremities, Genotype, Male, Mice, Mice, Inbred C57BL, Mice, Knockout, Neutropenia, Osteoblasts, Osteogenesis, Osteoporosis, Osteoprotegerin, Pasteurellaceae, RANK Ligand, Transcription Factors, Trichomonas, Journal Article, Research Support, Non-U.S. Gov't",
author = "Sven Geissler and Martin Textor and Sabine Stumpp and Sebastian Seitz and Anja Lekaj and Sabrina Brunk and Sabine Klaassen and Thorsten Schinke and Christoph Klein and Stefan Mundlos and Uwe Kornak and Jirko K{\"u}hnisch",
year = "2018",
doi = "10.1371/journal.pone.0198510",
language = "English",
volume = "13",
pages = "e0198510",
journal = "PLOS ONE",
issn = "1932-6203",
publisher = "Public Library of Science",
number = "6",

}

RIS

TY - JOUR

T1 - Loss of murine Gfi1 causes neutropenia and induces osteoporosis depending on the pathogen load and systemic inflammation

AU - Geissler, Sven

AU - Textor, Martin

AU - Stumpp, Sabine

AU - Seitz, Sebastian

AU - Lekaj, Anja

AU - Brunk, Sabrina

AU - Klaassen, Sabine

AU - Schinke, Thorsten

AU - Klein, Christoph

AU - Mundlos, Stefan

AU - Kornak, Uwe

AU - Kühnisch, Jirko

PY - 2018

Y1 - 2018

N2 - Gfi1 is a key molecule in hematopoietic lineage development and mutations in GFI1 cause severe congenital neutropenia (SCN). Neutropenia is associated with low bone mass, but the underlying mechanisms are poorly characterized. Using Gfi1 knock-out mice (Gfi1-ko/ko) as SCN model, we studied the relationship between neutropenia and bone mass upon different pathogen load conditions. Our analysis reveals that Gfi1-ko/ko mice kept under strict specific pathogen free (SPF) conditions demonstrate normal bone mass and survival. However, Gfi1-ko/ko mice with early (nonSPF) or late (SPF+nonSPF) pathogen exposure develop low bone mass. Gfi1-ko/ko mice demonstrate a striking rise of systemic inflammatory markers according to elevated pathogen exposure and reduced bone mass. Elevated inflammatory cytokines include for instance Il-1b, Il-6, and Tnf-alpha that regulate osteoclast development. We conclude that low bone mass, due to low neutrophil counts, is caused by the degree of systemic inflammation promoting osteoclastogenesis.

AB - Gfi1 is a key molecule in hematopoietic lineage development and mutations in GFI1 cause severe congenital neutropenia (SCN). Neutropenia is associated with low bone mass, but the underlying mechanisms are poorly characterized. Using Gfi1 knock-out mice (Gfi1-ko/ko) as SCN model, we studied the relationship between neutropenia and bone mass upon different pathogen load conditions. Our analysis reveals that Gfi1-ko/ko mice kept under strict specific pathogen free (SPF) conditions demonstrate normal bone mass and survival. However, Gfi1-ko/ko mice with early (nonSPF) or late (SPF+nonSPF) pathogen exposure develop low bone mass. Gfi1-ko/ko mice demonstrate a striking rise of systemic inflammatory markers according to elevated pathogen exposure and reduced bone mass. Elevated inflammatory cytokines include for instance Il-1b, Il-6, and Tnf-alpha that regulate osteoclast development. We conclude that low bone mass, due to low neutrophil counts, is caused by the degree of systemic inflammation promoting osteoclastogenesis.

KW - Animals

KW - Body Weight

KW - Bone and Bones

KW - Cell Differentiation

KW - Cytokines

KW - DNA-Binding Proteins

KW - Extremities

KW - Genotype

KW - Male

KW - Mice

KW - Mice, Inbred C57BL

KW - Mice, Knockout

KW - Neutropenia

KW - Osteoblasts

KW - Osteogenesis

KW - Osteoporosis

KW - Osteoprotegerin

KW - Pasteurellaceae

KW - RANK Ligand

KW - Transcription Factors

KW - Trichomonas

KW - Journal Article

KW - Research Support, Non-U.S. Gov't

U2 - 10.1371/journal.pone.0198510

DO - 10.1371/journal.pone.0198510

M3 - SCORING: Journal article

C2 - 29879182

VL - 13

SP - e0198510

JO - PLOS ONE

JF - PLOS ONE

SN - 1932-6203

IS - 6

ER -