{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T17:52:26Z","timestamp":1785520346566,"version":"3.56.0"},"reference-count":55,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"848","funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["KE 2179\/10-1"],"award-info":[{"award-number":["KE 2179\/10-1"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["KFO 5029 KE 2179\/11"],"award-info":[{"award-number":["KFO 5029 KE 2179\/11"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["BA 7863\/1-1"],"award-info":[{"award-number":["BA 7863\/1-1"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.science.org"],"crossmark-restriction":true},"short-container-title":["Sci. Transl. Med."],"published-print":{"date-parts":[[2026,5,6]]},"abstract":"<jats:p>\n                    After musculoskeletal injury, a considerable proportion of patients develop heterotopic ossification (HO), the formation of bone at ectopic sites. Traumatic HO is a disabling condition, potentially resulting in loss of joint function and compression of neurovascular structures. Available treatment options are often unsuccessful, frequently necessitating surgical resection of HO lesions with a high risk of recurrence. Given that myeloid cells, including neutrophils and macrophages, are among the first cell types to infiltrate injured tissue, the present study explored the relationship of extracellular traps (ETs) with HO formation in humans and mice. Human HO sample analysis revealed the presence of different stages of ETosis, which are clinically associated with increased ET concentrations in the blood. Experimentally, genetic impairment of ET resolution through combined\n                    <jats:italic toggle=\"yes\">DNase1<\/jats:italic>\n                    and\n                    <jats:italic toggle=\"yes\">DNase1l3<\/jats:italic>\n                    deficiency led to increased traumatic HO in mice, whereas HO was strongly attenuated by additional deletion of the ET generator\n                    <jats:italic toggle=\"yes\">Padi4<\/jats:italic>\n                    . Neutrophil depletion impaired local ET formation, reduced HO formation, and blunted genotype-specific differences in HO outcome. In osteogenic precursors, ETs promoted matrix mineralization, and inhibition of ETosis or degradation of cell-free DNA, a major ET component, resulted in reduced osteogenesis. Pharmacological facilitation of ET clearance by dornase alfa, a US Food and Drug Administration\u2013approved recombinant DNase1, or inhibition of ETs by the PADI4 inhibitor GSK484, resulted in inhibition of traumatic HO formation in mice without adversely affecting systemic bone remodeling. Together, our clinical and experimental findings demonstrate that traumatic HO is mediated by targetable neutrophil-dependent mechanisms, with altered ET formation contributing to these effects.\n                  <\/jats:p>","DOI":"10.1126\/scitranslmed.ady4761","type":"journal-article","created":{"date-parts":[[2026,5,6]],"date-time":"2026-05-06T17:59:53Z","timestamp":1778090393000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":1,"title":["Extracellular traps from myeloid cells as therapeutic targets in traumatic heterotopic ossification"],"prefix":"10.1126","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1545-2152","authenticated-orcid":true,"given":"Shan","family":"Jiang","sequence":"first","affiliation":[{"name":"Department of Trauma and Orthopedic Surgery, University Medical Center Hamburg-Eppendorf, 20251 Hamburg, 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