Macrophage-derived oncostatin M contributes to human and mouse neurogenic heterotopic ossifications.
Identifieur interne : 000856 ( Main/Exploration ); précédent : 000855; suivant : 000857Macrophage-derived oncostatin M contributes to human and mouse neurogenic heterotopic ossifications.
Auteurs : Frédéric Torossian [France] ; Bernadette Guerton [France] ; Adrienne Anginot [France] ; Kylie A. Alexander [Australie] ; Christophe Desterke [France] ; Sabrina Soave [France] ; Hsu-Wen Tseng [Australie] ; Nassim Arouche [France] ; Laetitia Boutin [France] ; Irina Kulina [Australie] ; Marjorie Salga [Australie] ; Beulah Jose [Australie] ; Allison R. Pettit [Australie] ; Denis Clay [France] ; Nathalie Rochet [France] ; Erica Vlachos [France] ; Guillaume Genet [France] ; Charlotte Debaud [France] ; Philippe Denormandie [France] ; François Genet [France] ; Natalie A. Sims [Australie] ; Sébastien Banzet [France] ; Jean-Pierre Levesque [Australie] ; Jean-Jacques Lataillade [France] ; Marie-Caroline Le Bousse-Kerdilès [France]Source :
- JCI insight [ 2379-3708 ] ; 2017.
Abstract
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.
DOI: 10.1172/jci.insight.96034
PubMed: 29093266
Affiliations:
- Australie, France
- Provence-Alpes-Côte d'Azur, Victoria (État), Île-de-France
- Melbourne, Nice, Versailles
- Université de Melbourne, Université de Versailles-Saint-Quentin-en-Yvelines
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11 University, Paul Brousse Hospital, Villejuif, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Inserm UMR-S-MD1197, Paris 11 University, Paul Brousse Hospital, Villejuif</wicri:regionArea><wicri:noRegion>Villejuif</wicri:noRegion><wicri:noRegion>Villejuif</wicri:noRegion></affiliation></author><author><name sortKey="Kulina, Irina" sort="Kulina, Irina" uniqKey="Kulina I" first="Irina" last="Kulina">Irina Kulina</name><affiliation wicri:level="1"><nlm:affiliation>Mater Research Institute, The University of Queensland, Translational Research Institute, Woolloongabba, Queensland, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>Mater Research Institute, The University of Queensland, Translational Research Institute, Woolloongabba, Queensland</wicri:regionArea><wicri:noRegion>Queensland</wicri:noRegion></affiliation></author><author><name sortKey="Salga, Marjorie" sort="Salga, Marjorie" uniqKey="Salga M" 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Montigny le Bretonneux, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Université de Versailles Saint-Quentin-en-Yvelines, Evolution of neuromuscular diseases: innovative concepts and practices, Inserm U1179, Montigny le Bretonneux</wicri:regionArea><wicri:noRegion>Montigny le Bretonneux</wicri:noRegion><orgName type="university">Université de Versailles-Saint-Quentin-en-Yvelines</orgName><placeName><settlement type="city">Versailles</settlement><region type="region" nuts="2">Île-de-France</region></placeName></affiliation></author><author><name sortKey="Denormandie, Philippe" sort="Denormandie, Philippe" uniqKey="Denormandie P" first="Philippe" last="Denormandie">Philippe Denormandie</name><affiliation wicri:level="1"><nlm:affiliation>Service de Médecine Physique et de Réadaptation, Paris 12 University, Garches, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Service de Médecine Physique et de Réadaptation, Paris 12 University, Garches</wicri:regionArea><wicri:noRegion>Garches</wicri:noRegion><wicri:noRegion>Garches</wicri:noRegion></affiliation></author><author><name sortKey="Genet, Francois" sort="Genet, Francois" uniqKey="Genet F" first="François" last="Genet">François Genet</name><affiliation wicri:level="4"><nlm:affiliation>Université de Versailles Saint-Quentin-en-Yvelines, Evolution of neuromuscular diseases: innovative concepts and practices, Inserm U1179, Montigny le Bretonneux, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Université de Versailles Saint-Quentin-en-Yvelines, Evolution of neuromuscular diseases: innovative concepts and practices, Inserm U1179, Montigny le Bretonneux</wicri:regionArea><wicri:noRegion>Montigny le Bretonneux</wicri:noRegion><orgName type="university">Université de Versailles-Saint-Quentin-en-Yvelines</orgName><placeName><settlement type="city">Versailles</settlement><region type="region" 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Sims</name><affiliation wicri:level="4"><nlm:affiliation>St. Vincent's Institute of Medical Research and Department of Medicine, St. Vincent's Hospital, The University of Melbourne, Fitzroy, Victoria, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>St. Vincent's Institute of Medical Research and Department of Medicine, St. Vincent's Hospital, The University of Melbourne, Fitzroy, Victoria</wicri:regionArea><orgName type="university">Université de Melbourne</orgName><placeName><settlement type="city">Melbourne</settlement><region type="état">Victoria (État)</region></placeName></affiliation></author><author><name sortKey="Banzet, Sebastien" sort="Banzet, Sebastien" uniqKey="Banzet S" first="Sébastien" last="Banzet">Sébastien Banzet</name><affiliation wicri:level="1"><nlm:affiliation>Inserm UMR-S-MD1197, Paris 11 University, Paul Brousse Hospital, Villejuif, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Inserm 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wicri:level="1"><nlm:affiliation>Inserm UMR-S-MD1197, Paris 11 University, Paul Brousse Hospital, Villejuif, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Inserm UMR-S-MD1197, Paris 11 University, Paul Brousse Hospital, Villejuif</wicri:regionArea><wicri:noRegion>Villejuif</wicri:noRegion><wicri:noRegion>Villejuif</wicri:noRegion></affiliation></author><author><name sortKey="Le Bousse Kerdiles, Marie Caroline" sort="Le Bousse Kerdiles, Marie Caroline" uniqKey="Le Bousse Kerdiles M" first="Marie-Caroline" last="Le Bousse-Kerdilès">Marie-Caroline Le Bousse-Kerdilès</name><affiliation wicri:level="1"><nlm:affiliation>Inserm UMR-S-MD1197, Paris 11 University, Paul Brousse Hospital, Villejuif, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Inserm UMR-S-MD1197, Paris 11 University, Paul Brousse Hospital, Villejuif</wicri:regionArea><wicri:noRegion>Villejuif</wicri:noRegion><wicri:noRegion>Villejuif</wicri:noRegion></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2017">2017</date><idno type="RBID">pubmed:29093266</idno><idno type="pmid">29093266</idno><idno type="doi">10.1172/jci.insight.96034</idno><idno type="wicri:Area/PubMed/Corpus">000045</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">000045</idno><idno type="wicri:Area/PubMed/Curation">000045</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Curation">000045</idno><idno type="wicri:Area/PubMed/Checkpoint">000045</idno><idno type="wicri:explorRef" wicri:stream="Checkpoint" wicri:step="PubMed">000045</idno><idno type="wicri:Area/Ncbi/Merge">005137</idno><idno type="wicri:Area/Ncbi/Curation">005137</idno><idno type="wicri:Area/Ncbi/Checkpoint">005137</idno><idno type="wicri:Area/Main/Merge">000851</idno><idno type="wicri:Area/Main/Curation">000856</idno><idno type="wicri:Area/Main/Exploration">000856</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">Macrophage-derived oncostatin M contributes to human and mouse neurogenic heterotopic ossifications.</title><author><name sortKey="Torossian, Frederic" sort="Torossian, Frederic" uniqKey="Torossian F" first="Frédéric" last="Torossian">Frédéric Torossian</name><affiliation wicri:level="1"><nlm:affiliation>Inserm UMR-S-MD1197, Paris 11 University, Paul Brousse Hospital, Villejuif, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Inserm UMR-S-MD1197, Paris 11 University, Paul Brousse Hospital, Villejuif</wicri:regionArea><wicri:noRegion>Villejuif</wicri:noRegion><wicri:noRegion>Villejuif</wicri:noRegion></affiliation></author><author><name sortKey="Guerton, Bernadette" sort="Guerton, Bernadette" uniqKey="Guerton B" first="Bernadette" last="Guerton">Bernadette Guerton</name><affiliation wicri:level="1"><nlm:affiliation>Inserm UMR-S-MD1197, Paris 11 University, Paul Brousse Hospital, Villejuif, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Inserm UMR-S-MD1197, Paris 11 University, Paul Brousse Hospital, Villejuif</wicri:regionArea><wicri:noRegion>Villejuif</wicri:noRegion><wicri:noRegion>Villejuif</wicri:noRegion></affiliation></author><author><name sortKey="Anginot, Adrienne" sort="Anginot, Adrienne" uniqKey="Anginot A" first="Adrienne" last="Anginot">Adrienne Anginot</name><affiliation wicri:level="1"><nlm:affiliation>Inserm UMR-S-MD1197, Paris 11 University, Paul Brousse Hospital, Villejuif, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Inserm UMR-S-MD1197, Paris 11 University, Paul Brousse Hospital, Villejuif</wicri:regionArea><wicri:noRegion>Villejuif</wicri:noRegion><wicri:noRegion>Villejuif</wicri:noRegion></affiliation></author><author><name sortKey="Alexander, Kylie A" sort="Alexander, Kylie A" uniqKey="Alexander K" first="Kylie A" last="Alexander">Kylie A. Alexander</name><affiliation wicri:level="1"><nlm:affiliation>Mater Research Institute, The University of Queensland, Translational Research Institute, Woolloongabba, Queensland, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>Mater Research Institute, The University of Queensland, Translational Research Institute, Woolloongabba, Queensland</wicri:regionArea><wicri:noRegion>Queensland</wicri:noRegion></affiliation></author><author><name sortKey="Desterke, Christophe" sort="Desterke, Christophe" uniqKey="Desterke C" first="Christophe" last="Desterke">Christophe Desterke</name><affiliation wicri:level="1"><nlm:affiliation>UMS33, Paris 11 University, Paul Brousse Hospital, Villejuif, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>UMS33, Paris 11 University, Paul Brousse Hospital, Villejuif</wicri:regionArea><wicri:noRegion>Villejuif</wicri:noRegion><wicri:noRegion>Villejuif</wicri:noRegion></affiliation></author><author><name sortKey="Soave, Sabrina" sort="Soave, Sabrina" uniqKey="Soave S" first="Sabrina" last="Soave">Sabrina Soave</name><affiliation wicri:level="1"><nlm:affiliation>Inserm UMR-S-MD1197, Paris 11 University, Paul Brousse Hospital, Villejuif, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Inserm UMR-S-MD1197, Paris 11 University, Paul Brousse Hospital, Villejuif</wicri:regionArea><wicri:noRegion>Villejuif</wicri:noRegion><wicri:noRegion>Villejuif</wicri:noRegion></affiliation></author><author><name sortKey="Tseng, Hsu Wen" sort="Tseng, Hsu Wen" uniqKey="Tseng H" first="Hsu-Wen" last="Tseng">Hsu-Wen Tseng</name><affiliation wicri:level="1"><nlm:affiliation>Mater Research Institute, The University of Queensland, Translational Research Institute, Woolloongabba, Queensland, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>Mater Research Institute, The University of Queensland, Translational Research Institute, Woolloongabba, Queensland</wicri:regionArea><wicri:noRegion>Queensland</wicri:noRegion></affiliation></author><author><name sortKey="Arouche, Nassim" sort="Arouche, Nassim" uniqKey="Arouche N" first="Nassim" last="Arouche">Nassim Arouche</name><affiliation wicri:level="1"><nlm:affiliation>Inserm UMR-S-MD1197, Paris 11 University, Paul Brousse Hospital, Villejuif, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Inserm UMR-S-MD1197, Paris 11 University, Paul Brousse Hospital, Villejuif</wicri:regionArea><wicri:noRegion>Villejuif</wicri:noRegion><wicri:noRegion>Villejuif</wicri:noRegion></affiliation></author><author><name sortKey="Boutin, Laetitia" sort="Boutin, Laetitia" uniqKey="Boutin L" first="Laetitia" last="Boutin">Laetitia Boutin</name><affiliation wicri:level="1"><nlm:affiliation>Inserm UMR-S-MD1197, Paris 11 University, Paul Brousse Hospital, Villejuif, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Inserm UMR-S-MD1197, Paris 11 University, Paul Brousse Hospital, Villejuif</wicri:regionArea><wicri:noRegion>Villejuif</wicri:noRegion><wicri:noRegion>Villejuif</wicri:noRegion></affiliation></author><author><name sortKey="Kulina, Irina" sort="Kulina, Irina" uniqKey="Kulina I" first="Irina" last="Kulina">Irina Kulina</name><affiliation wicri:level="1"><nlm:affiliation>Mater Research Institute, The University of Queensland, Translational Research Institute, Woolloongabba, Queensland, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>Mater Research Institute, The University of Queensland, Translational Research Institute, Woolloongabba, Queensland</wicri:regionArea><wicri:noRegion>Queensland</wicri:noRegion></affiliation></author><author><name sortKey="Salga, Marjorie" sort="Salga, Marjorie" uniqKey="Salga M" first="Marjorie" last="Salga">Marjorie Salga</name><affiliation wicri:level="1"><nlm:affiliation>Mater Research Institute, The University of Queensland, Translational Research Institute, Woolloongabba, Queensland, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>Mater Research Institute, The University of Queensland, Translational Research Institute, Woolloongabba, Queensland</wicri:regionArea><wicri:noRegion>Queensland</wicri:noRegion></affiliation></author><author><name sortKey="Jose, Beulah" sort="Jose, Beulah" uniqKey="Jose B" first="Beulah" last="Jose">Beulah Jose</name><affiliation wicri:level="1"><nlm:affiliation>Mater Research Institute, The University of Queensland, Translational Research Institute, Woolloongabba, Queensland, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>Mater Research Institute, The University of Queensland, Translational Research Institute, Woolloongabba, Queensland</wicri:regionArea><wicri:noRegion>Queensland</wicri:noRegion></affiliation></author><author><name sortKey="Pettit, Allison R" sort="Pettit, Allison R" uniqKey="Pettit A" first="Allison R" last="Pettit">Allison R. Pettit</name><affiliation wicri:level="1"><nlm:affiliation>Mater Research Institute, The University of Queensland, Translational Research Institute, Woolloongabba, Queensland, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>Mater Research Institute, The University of Queensland, Translational Research Institute, Woolloongabba, Queensland</wicri:regionArea><wicri:noRegion>Queensland</wicri:noRegion></affiliation></author><author><name sortKey="Clay, Denis" sort="Clay, Denis" uniqKey="Clay D" first="Denis" last="Clay">Denis Clay</name><affiliation wicri:level="1"><nlm:affiliation>UMS33, Paris 11 University, Paul Brousse Hospital, Villejuif, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>UMS33, Paris 11 University, Paul Brousse Hospital, Villejuif</wicri:regionArea><wicri:noRegion>Villejuif</wicri:noRegion><wicri:noRegion>Villejuif</wicri:noRegion></affiliation></author><author><name sortKey="Rochet, Nathalie" sort="Rochet, Nathalie" uniqKey="Rochet N" first="Nathalie" last="Rochet">Nathalie Rochet</name><affiliation wicri:level="3"><nlm:affiliation>Université Côte d'Azur, CNRS, Inserm, Institut de Biologie Valrose, Nice, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Université Côte d'Azur, CNRS, Inserm, Institut de Biologie Valrose, Nice</wicri:regionArea><placeName><region type="region">Provence-Alpes-Côte d'Azur</region><region type="old region">Provence-Alpes-Côte d'Azur</region><settlement type="city">Nice</settlement></placeName></affiliation></author><author><name sortKey="Vlachos, Erica" sort="Vlachos, Erica" uniqKey="Vlachos E" first="Erica" last="Vlachos">Erica Vlachos</name><affiliation wicri:level="1"><nlm:affiliation>Service de Médecine Physique et de Réadaptation, Paris 12 University, Garches, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Service de Médecine Physique et de Réadaptation, Paris 12 University, Garches</wicri:regionArea><wicri:noRegion>Garches</wicri:noRegion><wicri:noRegion>Garches</wicri:noRegion></affiliation></author><author><name sortKey="Genet, Guillaume" sort="Genet, Guillaume" uniqKey="Genet G" first="Guillaume" last="Genet">Guillaume Genet</name><affiliation wicri:level="1"><nlm:affiliation>Service de Médecine Physique et de Réadaptation, Paris 12 University, Garches, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Service de Médecine Physique et de Réadaptation, Paris 12 University, Garches</wicri:regionArea><wicri:noRegion>Garches</wicri:noRegion><wicri:noRegion>Garches</wicri:noRegion></affiliation></author><author><name sortKey="Debaud, Charlotte" sort="Debaud, Charlotte" uniqKey="Debaud C" first="Charlotte" last="Debaud">Charlotte Debaud</name><affiliation wicri:level="4"><nlm:affiliation>Université de Versailles Saint-Quentin-en-Yvelines, Evolution of neuromuscular diseases: innovative concepts and practices, Inserm U1179, Montigny le Bretonneux, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Université de Versailles Saint-Quentin-en-Yvelines, Evolution of neuromuscular diseases: innovative concepts and practices, Inserm U1179, Montigny le Bretonneux</wicri:regionArea><wicri:noRegion>Montigny le Bretonneux</wicri:noRegion><orgName type="university">Université de Versailles-Saint-Quentin-en-Yvelines</orgName><placeName><settlement type="city">Versailles</settlement><region type="region" nuts="2">Île-de-France</region></placeName></affiliation></author><author><name sortKey="Denormandie, Philippe" sort="Denormandie, Philippe" uniqKey="Denormandie P" first="Philippe" last="Denormandie">Philippe Denormandie</name><affiliation wicri:level="1"><nlm:affiliation>Service de Médecine Physique et de Réadaptation, Paris 12 University, Garches, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Service de Médecine Physique et de Réadaptation, Paris 12 University, Garches</wicri:regionArea><wicri:noRegion>Garches</wicri:noRegion><wicri:noRegion>Garches</wicri:noRegion></affiliation></author><author><name sortKey="Genet, Francois" sort="Genet, Francois" uniqKey="Genet F" first="François" last="Genet">François Genet</name><affiliation wicri:level="4"><nlm:affiliation>Université de Versailles Saint-Quentin-en-Yvelines, Evolution of neuromuscular diseases: innovative concepts and practices, Inserm U1179, Montigny le Bretonneux, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Université de Versailles Saint-Quentin-en-Yvelines, Evolution of neuromuscular diseases: innovative concepts and practices, Inserm U1179, Montigny le Bretonneux</wicri:regionArea><wicri:noRegion>Montigny le Bretonneux</wicri:noRegion><orgName type="university">Université de Versailles-Saint-Quentin-en-Yvelines</orgName><placeName><settlement type="city">Versailles</settlement><region type="region" nuts="2">Île-de-France</region></placeName></affiliation></author><author><name sortKey="Sims, Natalie A" sort="Sims, Natalie A" uniqKey="Sims N" first="Natalie A" last="Sims">Natalie A. Sims</name><affiliation wicri:level="4"><nlm:affiliation>St. Vincent's Institute of Medical Research and Department of Medicine, St. Vincent's Hospital, The University of Melbourne, Fitzroy, Victoria, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>St. Vincent's Institute of Medical Research and Department of Medicine, St. Vincent's Hospital, The University of Melbourne, Fitzroy, Victoria</wicri:regionArea><orgName type="university">Université de Melbourne</orgName><placeName><settlement type="city">Melbourne</settlement><region type="état">Victoria (État)</region></placeName></affiliation></author><author><name sortKey="Banzet, Sebastien" sort="Banzet, Sebastien" uniqKey="Banzet S" first="Sébastien" last="Banzet">Sébastien Banzet</name><affiliation wicri:level="1"><nlm:affiliation>Inserm UMR-S-MD1197, Paris 11 University, Paul Brousse Hospital, Villejuif, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Inserm UMR-S-MD1197, Paris 11 University, Paul Brousse Hospital, Villejuif</wicri:regionArea><wicri:noRegion>Villejuif</wicri:noRegion><wicri:noRegion>Villejuif</wicri:noRegion></affiliation></author><author><name sortKey="Levesque, Jean Pierre" sort="Levesque, Jean Pierre" uniqKey="Levesque J" first="Jean-Pierre" last="Levesque">Jean-Pierre Levesque</name><affiliation wicri:level="1"><nlm:affiliation>Mater Research Institute, The University of Queensland, Translational Research Institute, Woolloongabba, Queensland, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>Mater Research Institute, The University of Queensland, Translational Research Institute, Woolloongabba, Queensland</wicri:regionArea><wicri:noRegion>Queensland</wicri:noRegion></affiliation></author><author><name sortKey="Lataillade, Jean Jacques" sort="Lataillade, Jean Jacques" uniqKey="Lataillade J" first="Jean-Jacques" last="Lataillade">Jean-Jacques Lataillade</name><affiliation wicri:level="1"><nlm:affiliation>Inserm UMR-S-MD1197, Paris 11 University, Paul Brousse Hospital, Villejuif, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Inserm UMR-S-MD1197, Paris 11 University, Paul Brousse Hospital, Villejuif</wicri:regionArea><wicri:noRegion>Villejuif</wicri:noRegion><wicri:noRegion>Villejuif</wicri:noRegion></affiliation></author><author><name sortKey="Le Bousse Kerdiles, Marie Caroline" sort="Le Bousse Kerdiles, Marie Caroline" uniqKey="Le Bousse Kerdiles M" first="Marie-Caroline" last="Le Bousse-Kerdilès">Marie-Caroline Le Bousse-Kerdilès</name><affiliation wicri:level="1"><nlm:affiliation>Inserm UMR-S-MD1197, Paris 11 University, Paul Brousse Hospital, Villejuif, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Inserm UMR-S-MD1197, Paris 11 University, Paul Brousse Hospital, Villejuif</wicri:regionArea><wicri:noRegion>Villejuif</wicri:noRegion><wicri:noRegion>Villejuif</wicri:noRegion></affiliation></author></analytic><series><title level="j">JCI insight</title><idno type="eISSN">2379-3708</idno><imprint><date when="2017" type="published">2017</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">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.</div></front></TEI><affiliations><list><country><li>Australie</li><li>France</li></country><region><li>Provence-Alpes-Côte d'Azur</li><li>Victoria (État)</li><li>Île-de-France</li></region><settlement><li>Melbourne</li><li>Nice</li><li>Versailles</li></settlement><orgName><li>Université de Melbourne</li><li>Université de Versailles-Saint-Quentin-en-Yvelines</li></orgName></list><tree><country name="France"><noRegion><name sortKey="Torossian, Frederic" sort="Torossian, Frederic" uniqKey="Torossian F" first="Frédéric" last="Torossian">Frédéric Torossian</name></noRegion><name sortKey="Anginot, Adrienne" sort="Anginot, Adrienne" uniqKey="Anginot A" first="Adrienne" last="Anginot">Adrienne Anginot</name><name sortKey="Arouche, Nassim" sort="Arouche, Nassim" uniqKey="Arouche N" first="Nassim" last="Arouche">Nassim Arouche</name><name sortKey="Banzet, Sebastien" sort="Banzet, Sebastien" uniqKey="Banzet S" first="Sébastien" last="Banzet">Sébastien Banzet</name><name sortKey="Boutin, Laetitia" sort="Boutin, Laetitia" uniqKey="Boutin L" first="Laetitia" last="Boutin">Laetitia Boutin</name><name sortKey="Clay, Denis" sort="Clay, Denis" uniqKey="Clay D" first="Denis" last="Clay">Denis Clay</name><name sortKey="Debaud, Charlotte" sort="Debaud, Charlotte" uniqKey="Debaud C" first="Charlotte" last="Debaud">Charlotte Debaud</name><name sortKey="Denormandie, Philippe" sort="Denormandie, Philippe" uniqKey="Denormandie P" first="Philippe" last="Denormandie">Philippe Denormandie</name><name sortKey="Desterke, Christophe" sort="Desterke, Christophe" uniqKey="Desterke C" first="Christophe" last="Desterke">Christophe Desterke</name><name sortKey="Genet, Francois" sort="Genet, Francois" uniqKey="Genet F" first="François" last="Genet">François Genet</name><name sortKey="Genet, Guillaume" sort="Genet, Guillaume" uniqKey="Genet G" first="Guillaume" last="Genet">Guillaume Genet</name><name sortKey="Guerton, Bernadette" sort="Guerton, Bernadette" uniqKey="Guerton B" first="Bernadette" last="Guerton">Bernadette Guerton</name><name sortKey="Lataillade, Jean Jacques" sort="Lataillade, Jean Jacques" uniqKey="Lataillade J" first="Jean-Jacques" last="Lataillade">Jean-Jacques Lataillade</name><name sortKey="Le Bousse Kerdiles, Marie Caroline" sort="Le Bousse Kerdiles, Marie Caroline" uniqKey="Le Bousse Kerdiles M" first="Marie-Caroline" last="Le Bousse-Kerdilès">Marie-Caroline Le Bousse-Kerdilès</name><name sortKey="Rochet, Nathalie" sort="Rochet, Nathalie" uniqKey="Rochet N" first="Nathalie" last="Rochet">Nathalie Rochet</name><name sortKey="Soave, Sabrina" sort="Soave, Sabrina" uniqKey="Soave S" first="Sabrina" last="Soave">Sabrina Soave</name><name sortKey="Vlachos, Erica" sort="Vlachos, Erica" uniqKey="Vlachos E" first="Erica" last="Vlachos">Erica Vlachos</name></country><country name="Australie"><noRegion><name sortKey="Alexander, Kylie A" sort="Alexander, Kylie A" uniqKey="Alexander K" first="Kylie A" last="Alexander">Kylie A. Alexander</name></noRegion><name sortKey="Jose, Beulah" sort="Jose, Beulah" uniqKey="Jose B" first="Beulah" last="Jose">Beulah Jose</name><name sortKey="Kulina, Irina" sort="Kulina, Irina" uniqKey="Kulina I" first="Irina" last="Kulina">Irina Kulina</name><name sortKey="Levesque, Jean Pierre" sort="Levesque, Jean Pierre" uniqKey="Levesque J" first="Jean-Pierre" last="Levesque">Jean-Pierre Levesque</name><name sortKey="Pettit, Allison R" sort="Pettit, Allison R" uniqKey="Pettit A" first="Allison R" last="Pettit">Allison R. Pettit</name><name sortKey="Salga, Marjorie" sort="Salga, Marjorie" uniqKey="Salga M" first="Marjorie" last="Salga">Marjorie Salga</name><name sortKey="Sims, Natalie A" sort="Sims, Natalie A" uniqKey="Sims N" first="Natalie A" last="Sims">Natalie A. Sims</name><name sortKey="Tseng, Hsu Wen" sort="Tseng, Hsu Wen" uniqKey="Tseng H" first="Hsu-Wen" last="Tseng">Hsu-Wen Tseng</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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