Fra-2 Expression in Osteoblasts Regulates Systemic Inflammation and Lung Injury through Osteopontin

Luo Y, Grötsch B, Hannemann N, Jimenez M, Ipseiz N, Uluckan O, Lin N, Schett G, Wagner EF, Bozec A (2018)

Publication Type: Journal article

Publication year: 2018

Journal

Molecular and Cellular Biology American Society for Microbiology

Book Volume: 38

Journal Issue: 22

DOI: 10.1128/MCB.00022-18

Abstract

Inflammatory responses require mobilization of innate immune cells from the bone marrow. The functionality of this process depends on the state of the bone marrow microenvironment. We therefore hypothesized that molecular changes in osteoblasts, which are essential stromal cells of the bone marrow microenvironment, influence the inflammatory response. Here, we show that osteoblast-specific expression of the AP-1 transcription factor Fra-2 (Fra-2Ob-tet) induced a systemic inflammatory state with infiltration of neutrophils and proinflammatory macrophages into the spleen and liver as well as increased levels of proinflammatory cytokines, such as interleukin-1β (IL-1β), IL-6, and granulocyte-macrophage colony-stimulating factor (GM-CSF). By in vivo inhibition of osteopontin (OPN) in Fra-2Ob-tet mice, we demonstrated that this process was dependent on OPN expression, which mediates alterations of the bone marrow niche. OPN expression was transcriptionally enhanced by Fra-2 and stimulated mesenchymal stem cell (MSC) expansion. Furthermore, in a murine lung injury model, Fra-2Ob-tet mice showed increased inflammatory responses and more severe disease features via an enhanced and sustained inflammatory response to lipopolysaccharide (LPS). Our findings demonstrate for the first time that molecular changes in osteoblasts influence the susceptibility to inflammation by altering evasion of innate immune cells from the bone marrow space.

Authors with CRIS profile

Georg Schett Lehrstuhl für Innere Medizin III Aline Bozec Juniorprofessur für Osteoimmunologie

Additional Organisation(s)

Interdisziplinäres Zentrum für Klinische Forschung

Involved external institutions

Banco Bilbao Vizcaya Argentaria (BBVA S.A.) ES Spain (ES)

How to cite

APA:

Luo, Y., Grötsch, B., Hannemann, N., Jimenez, M., Ipseiz, N., Uluckan, O.,... Bozec, A. (2018). Fra-2 Expression in Osteoblasts Regulates Systemic Inflammation and Lung Injury through Osteopontin. Molecular and Cellular Biology, 38(22). https://dx.doi.org/10.1128/MCB.00022-18

MLA:

Luo, Yubin, et al. "Fra-2 Expression in Osteoblasts Regulates Systemic Inflammation and Lung Injury through Osteopontin." Molecular and Cellular Biology 38.22 (2018).

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