Oncostatin M, an Inflammatory Cytokine Produced by Macrophages, Supports Intramembranous Bone Healing in a Mouse Model of Tibia Injury
| Autor: | Frédéric Blanchard, Dominique Heymann, Anne-Laure Gamblin, Pierre Layrolle, Bénédicte Brounais-Le Royer, Jérôme Amiaud, Pierre J. Guihard, Audrey Renaud, Marie-Astrid Boutet, Martine Berreur, Françoise Rédini |
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| Rok vydání: | 2015 |
| Předmět: |
STAT3 Transcription Factor
medicine.medical_treatment Osteoclasts Core Binding Factor Alpha 1 Subunit Oncostatin M Bone healing Bone resorption Pathology and Forensic Medicine Mice Osteogenesis medicine Animals Bone Resorption STAT3 Cell Proliferation Osteoblasts Tibia biology Bone Injury Chemistry Macrophages Receptors Oncostatin M Osteoblast Alkaline Phosphatase Cell biology Cytokine medicine.anatomical_structure Intramembranous ossification Immunology biology.protein |
| Zdroj: | The American Journal of Pathology. 185:765-775 |
| ISSN: | 0002-9440 |
| DOI: | 10.1016/j.ajpath.2014.11.008 |
| Popis: | Different macrophage depletion strategies have demonstrated a vital role of macrophages in bone healing, but the underlying molecular mechanisms are poorly understood. Here, with the use of a mouse model of tibia injury, we found that the cytokine oncostatin M [OSM or murine (m)OSM] was overexpressed during the initial inflammatory phase and that depletion of macrophages repressed mOSM expression. In Osm(-/-) mice, by micro-computed tomography and histology we observed a significant reduction in the amount of new intramedullar woven bone formed at the injured site, reduced number of Osterix(+) osteoblastic cells, and reduced expression of the osteoblast markers runt-related transcription factor 2 and alkaline phosphatase. In contrast, osteoclasts were normal throughout the healing period. One day after bone injury, Stat3, the main transcription factor activated by mOSM, was found phosphorylated/activated in endosteal osteoblastic cells located at the hedge of the hematoma. Interestingly, we observed reduced activation of Stat3 in Osm(-/-) mice. In addition, mice deficient in the mOSM receptor (Osmr(-/-)) also had reduced bone formation and osteoblast number within the injury site. These results suggest that mOSM, a product of macrophages, sustains intramembranous bone formation by signaling through Osmr and Stat3, acting on the recruitment, proliferation, and/or osteoblast differentiation of endosteal mesenchymal progenitor cells. Because bone resorption is largely unaltered, OSM could represent a new anabolic treatment for unconsolidated bone fractures. |
| Databáze: | OpenAIRE |
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