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PubMed Macrophage-derived oncostatin M contributes to human and mouse neurogenic heterotopic ossifications Neurogenic heterotopic ossification (NHO) is the formation of ectopic bone generally in muscles surrounding joints following spinal cord or brain injury. We investigated the mechanisms of NHO formation in 64 patients and a mouse model of spinal cord injury-induced NHO. We show that marrow from human NHOs contains hematopoietic stem cell (HSC) niches, in which mesenchymal stromal cells (MSCs) and endothelial cells provide an environment supporting HSC maintenance, proliferation, and differentiation. The transcriptomic signature of MSCs from NHOs shows a neuronal imprinting associated with a molecular network required for HSC support. We demonstrate that oncostatin M (OSM) produced by activated macrophages promotes osteoblastic differentiation and mineralization of human muscle-derived stromal cells surrounding NHOs. The key role of OSM was confirmed using an experimental model of NHO in mice defective for the OSM receptor (OSMR). Our results provide strong evidence that macrophages contribute to NHO formation through the osteogenic action of OSM on muscle cells within an inflammatory context and suggest that OSM/OSMR could be a suitable therapeutic target. Altogether, the evidence of HSCs in ectopic bones growing at the expense of soft tissue in spinal cord/brain-injured patients indicates that inflammation and muscle contribute to HSC regulation by the brain-bone-blood triad. eng 10.1172/jci.insight.96034 PMID: 29093266 2 21 Nov 02, 2017 JCI insight JCI Insight 2379-3708 Frédéric Torossian Bernadette Guerton Adrienne Anginot Kylie A. Alexander Christophe Desterke SabrinaSoave Hsu-WenTseng NassimArouche Laetitia Boutin IrinaKulina MarjorieSalga BeulahJose Allison R. Pettit DenisClay Nathalie Rochet EricaVlachos Guillaume Genet Charlotte Debaud Philippe Denormandie FrançoisGenet Natalie A. Sims Sébastien Banzet Jean-Pierre Levesque Jean-Jacques Lataillade Marie-Caroline Le Bousse-Kerdilès