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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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Item Type:Article
Title:Loss of murine Gfi1 causes neutropenia and induces osteoporosis depending on the pathogen load and systemic inflammation
Creators Name:Geissler, S. and Textor, M. and Stumpp, S. and Seitz, S. and Lekaj, A. and Brunk, S. and Klaassen, S. and Schinke, T. and Klein, C. and Mundlos, S. and Kornak, U. and Kühnisch, J.
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:Body Weight, Bone and Bones, Cell Differentiation, Cytokines, DNA-Binding Proteins, Extremities, Genotype, Inbred C57BL Mice, Knockout Mice, Neutropenia, Osteoblasts, Osteogenesis, Osteoporosis, Osteoprotegerin, Pasteurellaceae, RANK Ligand, Transcription Factors, Trichomonas, Animals, Mice
Source:PLoS ONE
ISSN:1932-6203
Publisher:Public Library of Science (U.S.A.)
Volume:13
Number:6
Page Range:e0198510
Date:7 June 2018
Official Publication:https://doi.org/10.1371/journal.pone.0198510
PubMed:View item in PubMed

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