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The mechanisms leading to NHO are incompletely understood and the only effective treatment to-date remains surgical resection. We previously established that several inflammatory pathways drive NHO pathogenesis in injured muscles in a mouse model of NHO and in humans. We also demonstrated a functional association between gram-negative bacterial infections and NHO development via lipopolysaccharide (LPS), a pathogen associated molecular pattern (PAMP), which exacerbated NHO in a Toll-like receptor-4 (TLR4)-dependent manner in mice.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Using our mouse model of NHO induced by SCI and muscle injury in mice, we tested the effect of a large array of purified PAMPs post-surgery to mimic fungal, viral and bacterial infections and measured NHO bone volumes by micro-computerized tomography (microCT). The effect of PAMPs was also tested in vitro on human muscle progenitors and monocyte\/macrophage populations.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Muscle progenitors and monocyte\/macrophage populations from humans and mice express numerous pattern recognition receptors. In mice, numerous PAMPs produced by bacteria, viruses and fungi exacerbated NHO formation, and the majority of these PAMPs indirectly stimulated fibro-adipogenic progenitor (FAP) calcium mineralization in vitro via macrophages. Likewise, in humans, some PAMPs, particularly those binding to TLR2, directly and indirectly increased the calcium mineralization and osteogenic differentiation of human FAPs isolated from muscles surrounding human NHO. Finally, we established that the indirect stimulation of human FAP mineralization was mediated by inflammatory cytokines IL-1 and oncostatin M secreted by monocytes in response to PAMPs. Overall, our findings suggest that numerous types of infection have the potential to exacerbate NHO development and further highlight the role of oncostatin M and IL-1 signaling pathways in NHO pathophysiology.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s12929-026-01237-y","type":"journal-article","created":{"date-parts":[[2026,4,10]],"date-time":"2026-04-10T09:17:06Z","timestamp":1775812626000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Many but not all pathogen-associated molecular patterns aggravate neurogenic heterotopic ossification after spinal cord injury"],"prefix":"10.1186","volume":"33","author":[{"given":"Selwin G.","family":"Samuel","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hsu-Wen","family":"Tseng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bastien","family":"Rival","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Val\u00e9rie","family":"Barbier","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kavita","family":"Bisht","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marjorie","family":"Salga","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shrutika M","family":"Mate","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Whitney","family":"Fleming","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fran\u00e7ois","family":"Gen\u00eat","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S\u00e9bastien","family":"Banzet","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jean-Pierre","family":"L\u00e9vesque","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Doroth\u00e9e","family":"Girard","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kylie A.","family":"Alexander","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2026,4,10]]},"reference":[{"key":"1237_CR1","doi-asserted-by":"publisher","first-page":"86","DOI":"10.1097\/00003086-198808000-00011","volume":"233","author":"DE Garland","year":"1988","unstructured":"Garland DE. 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