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The pathogenesis of NHO is poorly understood with no effective preventive treatment. The only curative treatment remains surgical resection of pathological NHOs. In a mouse model of SCI-induced NHO that involves a transection of the spinal cord combined with a muscle injury, a differential gene expression analysis revealed that genes involved in inflammation such as interleukin-1\u03b2 (IL-1\u03b2) were overexpressed in muscles developing NHO. Using mice knocked-out for the gene encoding IL-1 receptor (IL1R1) and neutralizing antibodies for IL-1\u03b1 and IL-1\u03b2, we show that IL-1 signaling contributes to NHO development after SCI in mice. Interestingly, other proteins involved in inflammation that were also overexpressed in muscles developing NHO, such as colony-stimulating factor-1, tumor necrosis factor, or C-C chemokine ligand-2, did not promote NHO development. Finally, using NHO biopsies from SCI and TBI patients, we show that IL-1\u03b2 is expressed by CD68+ macrophages. IL-1\u03b1 and IL-1\u03b2 produced by activated human monocytes promote calcium mineralization and RUNX2 expression in fibro-adipogenic progenitors isolated from muscles surrounding NHOs. Altogether, these data suggest that interleukin-1 promotes NHO development in both humans and mice. \u00a9 2021 American Society for Bone and Mineral Research (ASBMR).<\/jats:p>","DOI":"10.1002\/jbmr.4482","type":"journal-article","created":{"date-parts":[[2021,11,29]],"date-time":"2021-11-29T04:14:25Z","timestamp":1638159265000},"page":"531-546","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":40,"title":["Interleukin-1 Is Overexpressed in Injured Muscles Following Spinal Cord Injury and Promotes Neurogenic Heterotopic Ossification"],"prefix":"10.1093","volume":"37","author":[{"given":"Hsu-Wen","family":"Tseng","sequence":"first","affiliation":[{"name":"Mater Research Institute \u2013 The University of Queensland Woolloongabba Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irina","family":"Kulina","sequence":"additional","affiliation":[{"name":"Mater Research Institute \u2013 The University of 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