| Induction of Osteogenesis in Mesenchymal Stem Cells by Activated Monocytes/Macrophages Depends on Oncostatin M Signaling. | |
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MedLine Citation:
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PMID: 22267310 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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Bone resorption by osteoclasts and bone formation by osteoblasts are tightly coupled processes implicating factors in TNF, bone morphogenetic protein and Wnt families. In osteoimmunology, macrophages were described as another critical cell population regulating bone formation by osteoblasts but the coupling factors were not identified. Using a high throughput approach, we identified here Oncostatin M (OSM), a cytokine of the IL-6 family, as a major coupling factor produced by activated circulating CD14(+) or bone marrow CD11b(+) monocytes/macrophages that induces osteoblast differentiation and matrix mineralization from human mesenchymal stem cells (MSC) while inhibiting adipogenesis. Upon toll-like receptors (TLRs) activation by lipopolysaccharide or endogenous ligands, OSM was produced in classically activated inflammatory M1 and not M2 macrophages, through a cyclooxygenase-2 and prostaglandin-E2 regulatory loop. Stimulation of osteogenesis by activated monocytes/macrophages was prevented using neutralizing antibodies or siRNA to OSM, OSM receptor subunits gp130 and OSMR or to the downstream transcription factor STAT3. The induced osteoblast differentiation program culminated with enhanced expression of C/EBPδ (CCAAT-enhancer-binding protein δ), Cbfa1 and alkaline phosphatase. Overexpression of OSM in the tibia of mice has led to new bone apposition with no sign of bone resorption. Two other cytokines had also a potent role in bone formation induced by monocytes/macrophages and TLRs activation: IL-6 and Leukemia inhibitory factor. We propose that during bone inflammation, infection or injury, the IL-6 family signaling network activated by macrophages and TLR ligands stimulates bone formation that is largely uncoupled from bone resorption and is thus an important target for anabolic bone therapies. |
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Authors:
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Pierre Guihard; Yannic Danger; Bénédicte Brounais; Emmanuelle David; Régis Brion; Joël Delecrin; Carl D Richards; Sylvie Chevalier; Françoise Rédini; Dominique Heymann; Hugues Gascan; Frédéric Blanchard |
Publication Detail:
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Type: JOURNAL ARTICLE Date: 2012-1-20 |
Journal Detail:
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Title: Stem cells (Dayton, Ohio) Volume: - ISSN: 1549-4918 ISO Abbreviation: - Publication Date: 2012 Jan |
Date Detail:
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Created Date: 2012-1-23 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 9304532 Medline TA: Stem Cells Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Copyright Information:
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Copyright © 2012 AlphaMed Press. |
Affiliation:
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INSERM, UMR 957, Equipe Labellisée LIGUE 2012, Faculté de Médecine, F-44035 Nantes, France; Université de Nantes, Nantes Atlantique Universités, Laboratoire de Physiopathologie de la Résorption Osseuse et Thérapie des Tumeurs Osseuses Primitives, Faculté de Médecine, F-44035 Nantes, France. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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