Murine Oncostatin M Has Opposing Effects on the Proliferation of OP9 Bone Marrow Stromal Cells and NIH/3T3 Fibroblasts Signaling through the OSMR

The IL-6 family cytokine Oncostatin M (OSM) is involved in cell development, growth, hematopoiesis, inflammation, and cancer. Intriguingly, OSM has proliferative and antiproliferative effects depending on the target cell. The molecular mechanisms underlying these opposing effects are not fully under...

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Autores principales:	Lena Jakob, Tony Andreas Müller, Michael Rassner, Helen Kleinfelder, Pia Veratti, Jan Mitschke, Cornelius Miething, Robert A. J. Oostendorp, Dietmar Pfeifer, Miguel Waterhouse, Justus Duyster
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	mOSM proliferation JAK-STAT OSMR LIFR Biology (General) QH301-705.5 Chemistry QD1-999
Acceso en línea:	https://doaj.org/article/71c64d0264c8412aa6e6d7b528cfde00
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spelling	oai:doaj.org-article:71c64d0264c8412aa6e6d7b528cfde002021-11-11T17:07:15ZMurine Oncostatin M Has Opposing Effects on the Proliferation of OP9 Bone Marrow Stromal Cells and NIH/3T3 Fibroblasts Signaling through the OSMR10.3390/ijms2221116491422-00671661-6596https://doaj.org/article/71c64d0264c8412aa6e6d7b528cfde002021-10-01T00:00:00Zhttps://www.mdpi.com/1422-0067/22/21/11649https://doaj.org/toc/1661-6596https://doaj.org/toc/1422-0067The IL-6 family cytokine Oncostatin M (OSM) is involved in cell development, growth, hematopoiesis, inflammation, and cancer. Intriguingly, OSM has proliferative and antiproliferative effects depending on the target cell. The molecular mechanisms underlying these opposing effects are not fully understood. Previously, we found OSM upregulation in different myeloproliferative syndromes. However, OSM receptor (OSMR) expression was detected on stromal cells but not the malignant cells themselves. In the present study, we, therefore, investigated the effect of murine OSM (mOSM) on proliferation in stromal and fibroblast cell lines. We found that mOSM impairs the proliferation of bone marrow (BM) stromal cells, whereas fibroblasts responded to mOSM with increased proliferation. When we set out to reveal the mechanisms underlying these opposing effects, we detected increased expression of the OSM receptors OSMR and LIFR in stromal cells. Interestingly, <i>Osmr</i> knockdown and <i>Lifr</i> overexpression attenuated the OSM-mediated effect on proliferation in both cell lines indicating that mOSM affected the proliferation signaling mainly through the OSMR. Furthermore, mOSM induced activation of the JAK-STAT, PI3K-AKT, and MAPK-ERK pathways in OP9 and NIH/3T3 cells with differences in total protein levels between the two cell lines. Our findings offer new insights into the regulation of proliferation by mOSM.Lena JakobTony Andreas MüllerMichael RassnerHelen KleinfelderPia VerattiJan MitschkeCornelius MiethingRobert A. J. OostendorpDietmar PfeiferMiguel WaterhouseJustus DuysterMDPI AGarticlemOSMproliferationJAK-STATOSMRLIFRBiology (General)QH301-705.5ChemistryQD1-999ENInternational Journal of Molecular Sciences, Vol 22, Iss 11649, p 11649 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	mOSM proliferation JAK-STAT OSMR LIFR Biology (General) QH301-705.5 Chemistry QD1-999
spellingShingle	mOSM proliferation JAK-STAT OSMR LIFR Biology (General) QH301-705.5 Chemistry QD1-999 Lena Jakob Tony Andreas Müller Michael Rassner Helen Kleinfelder Pia Veratti Jan Mitschke Cornelius Miething Robert A. J. Oostendorp Dietmar Pfeifer Miguel Waterhouse Justus Duyster Murine Oncostatin M Has Opposing Effects on the Proliferation of OP9 Bone Marrow Stromal Cells and NIH/3T3 Fibroblasts Signaling through the OSMR
description	The IL-6 family cytokine Oncostatin M (OSM) is involved in cell development, growth, hematopoiesis, inflammation, and cancer. Intriguingly, OSM has proliferative and antiproliferative effects depending on the target cell. The molecular mechanisms underlying these opposing effects are not fully understood. Previously, we found OSM upregulation in different myeloproliferative syndromes. However, OSM receptor (OSMR) expression was detected on stromal cells but not the malignant cells themselves. In the present study, we, therefore, investigated the effect of murine OSM (mOSM) on proliferation in stromal and fibroblast cell lines. We found that mOSM impairs the proliferation of bone marrow (BM) stromal cells, whereas fibroblasts responded to mOSM with increased proliferation. When we set out to reveal the mechanisms underlying these opposing effects, we detected increased expression of the OSM receptors OSMR and LIFR in stromal cells. Interestingly, <i>Osmr</i> knockdown and <i>Lifr</i> overexpression attenuated the OSM-mediated effect on proliferation in both cell lines indicating that mOSM affected the proliferation signaling mainly through the OSMR. Furthermore, mOSM induced activation of the JAK-STAT, PI3K-AKT, and MAPK-ERK pathways in OP9 and NIH/3T3 cells with differences in total protein levels between the two cell lines. Our findings offer new insights into the regulation of proliferation by mOSM.
format	article
author	Lena Jakob Tony Andreas Müller Michael Rassner Helen Kleinfelder Pia Veratti Jan Mitschke Cornelius Miething Robert A. J. Oostendorp Dietmar Pfeifer Miguel Waterhouse Justus Duyster
author_facet	Lena Jakob Tony Andreas Müller Michael Rassner Helen Kleinfelder Pia Veratti Jan Mitschke Cornelius Miething Robert A. J. Oostendorp Dietmar Pfeifer Miguel Waterhouse Justus Duyster
author_sort	Lena Jakob
title	Murine Oncostatin M Has Opposing Effects on the Proliferation of OP9 Bone Marrow Stromal Cells and NIH/3T3 Fibroblasts Signaling through the OSMR
title_short	Murine Oncostatin M Has Opposing Effects on the Proliferation of OP9 Bone Marrow Stromal Cells and NIH/3T3 Fibroblasts Signaling through the OSMR
title_full	Murine Oncostatin M Has Opposing Effects on the Proliferation of OP9 Bone Marrow Stromal Cells and NIH/3T3 Fibroblasts Signaling through the OSMR
title_fullStr	Murine Oncostatin M Has Opposing Effects on the Proliferation of OP9 Bone Marrow Stromal Cells and NIH/3T3 Fibroblasts Signaling through the OSMR
title_full_unstemmed	Murine Oncostatin M Has Opposing Effects on the Proliferation of OP9 Bone Marrow Stromal Cells and NIH/3T3 Fibroblasts Signaling through the OSMR
title_sort	murine oncostatin m has opposing effects on the proliferation of op9 bone marrow stromal cells and nih/3t3 fibroblasts signaling through the osmr
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/71c64d0264c8412aa6e6d7b528cfde00
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Murine Oncostatin M Has Opposing Effects on the Proliferation of OP9 Bone Marrow Stromal Cells and NIH/3T3 Fibroblasts Signaling through the OSMR

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