Loss of murine Gfi1 causes neutropenia and induces osteoporosis depending on the pathogen load and systemic inflammation.
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 relat...
| _version_ | 1826579112013070336 |
|---|---|
| author | Sven Geissler Martin Textor Sabine Stumpp Sebastian Seitz Anja Lekaj Sabrina Brunk Sabine Klaassen Thorsten Schinke Christoph Klein Stefan Mundlos Uwe Kornak Jirko Kühnisch |
| author_facet | Sven Geissler Martin Textor Sabine Stumpp Sebastian Seitz Anja Lekaj Sabrina Brunk Sabine Klaassen Thorsten Schinke Christoph Klein Stefan Mundlos Uwe Kornak Jirko Kühnisch |
| author_sort | Sven Geissler |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-20T09:34:42Z |
| format | Article |
| id | doaj.art-264bdb4617e641ed968c635764215b6f |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2025-03-14T14:13:05Z |
| publishDate | 2018-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-264bdb4617e641ed968c635764215b6f2025-02-27T05:35:37ZengPublic Library of Science (PLoS)PLoS ONE1932-62032018-01-01136e019851010.1371/journal.pone.0198510Loss of murine Gfi1 causes neutropenia and induces osteoporosis depending on the pathogen load and systemic inflammation.Sven GeisslerMartin TextorSabine StumppSebastian SeitzAnja LekajSabrina BrunkSabine KlaassenThorsten SchinkeChristoph KleinStefan MundlosUwe KornakJirko KühnischGfi1 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.https://storage.googleapis.com/plos-corpus-prod/10.1371/journal.pone.0198510/1/pone.0198510.pdf?X-Goog-Algorithm=GOOG4-RSA-SHA256&X-Goog-Credential=wombat-sa%40plos-prod.iam.gserviceaccount.com%2F20210222%2Fauto%2Fstorage%2Fgoog4_request&X-Goog-Date=20210222T092029Z&X-Goog-Expires=3600&X-Goog-SignedHeaders=host&X-Goog-Signature=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 |
| spellingShingle | Sven Geissler Martin Textor Sabine Stumpp Sebastian Seitz Anja Lekaj Sabrina Brunk Sabine Klaassen Thorsten Schinke Christoph Klein Stefan Mundlos Uwe Kornak Jirko Kühnisch Loss of murine Gfi1 causes neutropenia and induces osteoporosis depending on the pathogen load and systemic inflammation. PLoS ONE |
| title | Loss of murine Gfi1 causes neutropenia and induces osteoporosis depending on the pathogen load and systemic inflammation. |
| title_full | Loss of murine Gfi1 causes neutropenia and induces osteoporosis depending on the pathogen load and systemic inflammation. |
| title_fullStr | Loss of murine Gfi1 causes neutropenia and induces osteoporosis depending on the pathogen load and systemic inflammation. |
| title_full_unstemmed | Loss of murine Gfi1 causes neutropenia and induces osteoporosis depending on the pathogen load and systemic inflammation. |
| title_short | Loss of murine Gfi1 causes neutropenia and induces osteoporosis depending on the pathogen load and systemic inflammation. |
| title_sort | loss of murine gfi1 causes neutropenia and induces osteoporosis depending on the pathogen load and systemic inflammation |
| url | https://storage.googleapis.com/plos-corpus-prod/10.1371/journal.pone.0198510/1/pone.0198510.pdf?X-Goog-Algorithm=GOOG4-RSA-SHA256&X-Goog-Credential=wombat-sa%40plos-prod.iam.gserviceaccount.com%2F20210222%2Fauto%2Fstorage%2Fgoog4_request&X-Goog-Date=20210222T092029Z&X-Goog-Expires=3600&X-Goog-SignedHeaders=host&X-Goog-Signature=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 |
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