{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T08:27:41Z","timestamp":1790497661050,"version":"4.1.0"},"reference-count":43,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2015,3,26]],"date-time":"2015-03-26T00:00:00Z","timestamp":1427328000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["1044091"],"award-info":[{"award-number":["1044091"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["1033736"],"award-info":[{"award-number":["1033736"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Assistance Publique \u2013 H\u00f4pitaux de Paris"},{"name":"Fondation BNP-Paribas"},{"name":"Forum for European-Australian Science and Technology Cooperation"},{"name":"Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale"},{"DOI":"10.13039\/501100014382","name":"IPSEN","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100014382","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100015471","name":"Mater Foundation","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100015471","id-type":"DOI","asserted-by":"crossref"}]},{"name":"merz"},{"name":"Service de Sant\u00e9 des Arm\u00e9es"},{"name":"Universit\u00e9 de Versailles Saint Quentin"}],"content-domain":{"domain":["pathsocjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Pathology"],"published-print":{"date-parts":[[2015,6]]},"abstract":"Abstract<\/jats:title>Neurological heterotopic ossification (NHO<\/jats:styled-content>) is the abnormal formation of bone in soft tissues as a consequence of spinal cord or traumatic brain injury. NHO<\/jats:styled-content> causes pain, ankyloses, vascular and nerve compression and delays rehabilitation in this high\u2010morbidity patient group. The pathological mechanisms leading to NHO<\/jats:styled-content> remain unknown and consequently there are no therapeutic options to prevent or reduce NHO<\/jats:styled-content>. Genetically modified mouse models of rare genetic forms of heterotopic ossification (HO<\/jats:styled-content>) exist, but their relevance to NHO<\/jats:styled-content> is questionable. Consequently, we developed the first model of spinal cord injury (SCI<\/jats:styled-content>)\u2010induced NHO<\/jats:styled-content> in genetically unmodified mice. Formation of NHO<\/jats:styled-content>, measured by micro\u2010computed tomography, required the combination of both SCI<\/jats:styled-content> and localized muscular inflammation. Our NHO<\/jats:styled-content> model faithfully reproduced many clinical features of NHO<\/jats:styled-content> in SCI<\/jats:styled-content> patients and both human and mouse NHO<\/jats:styled-content> tissues contained macrophages. Muscle\u2010derived mesenchymal progenitors underwent osteoblast differentiation in vitro<\/jats:italic> in response to serum from NHO<\/jats:styled-content> mice without additional exogenous osteogenic stimuli. Substance P was identified as a candidate NHO<\/jats:styled-content> systemic neuropeptide, as it was significantly elevated in the serum of NHO<\/jats:styled-content> patients. However, antagonism of substance P receptor in our NHO<\/jats:styled-content> model only modestly reduced the volume of NHO<\/jats:styled-content>. In contrast, ablation of phagocytic macrophages with clodronate\u2010loaded liposomes reduced the size of NHO<\/jats:styled-content> by 90%, supporting the conclusion that NHO<\/jats:styled-content> is highly dependent on inflammation and phagocytic macrophages in soft tissues. Overall, we have developed the first clinically relevant model of NHO<\/jats:styled-content> and demonstrated that a combined insult of neurological injury and soft tissue inflammation drives NHO<\/jats:styled-content> pathophysiology. Copyright \u00a9 2015 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.<\/jats:p>","DOI":"10.1002\/path.4519","type":"journal-article","created":{"date-parts":[[2015,2,25]],"date-time":"2015-02-25T01:25:10Z","timestamp":1424827510000},"page":"229-240","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":142,"title":["Neurological heterotopic ossification following spinal cord injury is triggered by macrophage\u2010mediated inflammation in muscle"],"prefix":"10.1002","volume":"236","author":[{"given":"Fran\u00e7ois","family":"Gen\u00eat","sequence":"first","affiliation":[{"name":"Blood and Bone Diseases Programme, Mater Research Institute University of Queensland Woolloongabba Australia"},{"name":"Department of Physical Medicine and Rehabilitation H\u00f4pital Raymond Poincar\u00e9 APHP, CIC\u2010IT 1429 Garches France"},{"name":"Universit\u00e9 Versailles Saint Quentin en Yvelines, END:ICAP U1179 INSERM, UFR des Sciences de la Sant\u00e9\u2013Simone Veil Montigny le Bretonneux France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irina","family":"Kulina","sequence":"additional","affiliation":[{"name":"Blood and Bone Diseases Programme, Mater Research Institute University of Queensland Woolloongabba Australia"},{"name":"School of Medicine University of Queensland Herston Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cedryck","family":"Vaquette","sequence":"additional","affiliation":[{"name":"Institute of Health Biomedical Innovation Queensland University of Technology Kelvin Grove Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fr\u00e9d\u00e9ric","family":"Torossian","sequence":"additional","affiliation":[{"name":"Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale Unit\u00e9 972 Villejuif France"},{"name":"Universit\u00e9 Paris\u2010Sud Institut Andr\u00e9 Lwoff Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan","family":"Millard","sequence":"additional","affiliation":[{"name":"Blood and Bone Diseases Programme, Mater Research Institute University of Queensland Woolloongabba Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Allison R","family":"Pettit","sequence":"additional","affiliation":[{"name":"Blood and Bone Diseases Programme, Mater Research Institute University of Queensland Woolloongabba Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalie A","family":"Sims","sequence":"additional","affiliation":[{"name":"St Vincent's Institute of Medical Research Fitzroy Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adrienne","family":"Anginot","sequence":"additional","affiliation":[{"name":"Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale Unit\u00e9 972 Villejuif France"},{"name":"Universit\u00e9 Paris\u2010Sud Institut Andr\u00e9 Lwoff Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernadette","family":"Guerton","sequence":"additional","affiliation":[{"name":"Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale Unit\u00e9 972 Villejuif France"},{"name":"Universit\u00e9 Paris\u2010Sud Institut Andr\u00e9 Lwoff Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ingrid G","family":"Winkler","sequence":"additional","affiliation":[{"name":"Blood and Bone Diseases Programme, Mater Research Institute University of Queensland Woolloongabba Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Val\u00e9rie","family":"Barbier","sequence":"additional","affiliation":[{"name":"Blood and Bone Diseases Programme, Mater Research Institute University of Queensland Woolloongabba Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean\u2010Jacques","family":"Lataillade","sequence":"additional","affiliation":[{"name":"Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale Unit\u00e9 972 Villejuif France"},{"name":"Centre de Transfusion Sanguine des Arm\u00e9es Clamart France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie\u2010Caroline","family":"Le Bousse\u2010Kerdil\u00e8s","sequence":"additional","affiliation":[{"name":"Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale Unit\u00e9 972 Villejuif France"},{"name":"Universit\u00e9 Paris\u2010Sud Institut Andr\u00e9 Lwoff Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dietmar W","family":"Hutmacher","sequence":"additional","affiliation":[{"name":"Blood and Bone Diseases Programme, Mater Research Institute University of Queensland Woolloongabba Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean\u2010Pierre","family":"Levesque","sequence":"additional","affiliation":[{"name":"Blood and Bone Diseases Programme, Mater Research Institute University of Queensland Woolloongabba Australia"},{"name":"School of Medicine University of Queensland Herston Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2015,3,26]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.sc.3100561"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.2106\/JBJS.H.00792"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.3233\/NRE-2011-0643"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/14651858.CD003321.pub3"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.3109\/02699052.2013.775490"},{"key":"e_1_2_7_7_1","first-page":"19","article-title":"Prevalence and risk factors of neurogenic heterotopic ossification in traumatic spinal cord and traumatic brain\u2010injured patients admitted to specialised units in Australia","volume":"14","author":"Reznik JE","year":"2014","journal-title":"J Musculoskelet Neuron Interact"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0016632"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1080\/16501970510027628"},{"key":"e_1_2_7_10_1","first-page":"293","article-title":"Deep venous thrombosis associated with heterotopic ossification","volume":"73","author":"Bradleigh LH","year":"1992","journal-title":"Arch Phys Med Rehabil"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00256-014-2003-6"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1097\/HTR.0b013e31822b54ba"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1302\/0301-620X.91B11.22305"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9440(10)63372-X"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1155\/2011\/309287"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng1783"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/jbmr.1637"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/0022-1759(94)90012-4"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.88.22.10208"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.exphem.2014.03.009"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1080\/10790268.2000.11753507"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00330-005-2769-y"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.sc.3100701"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/0003-9993(89)90003-8"},{"key":"e_1_2_7_25_1","article-title":"Experience with surgical resection of heterotopic bone in spinal cord injury patients","volume":"71","author":"Stover SL","year":"1991","journal-title":"Clin Orthop Relat Res"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncb2025"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1114758"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1080\/14653240600855905"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.ackd.2011.01.001"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcb.23225"},{"key":"e_1_2_7_31_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-60327-360-2_13"},{"key":"e_1_2_7_32_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2009-11-253534"},{"key":"e_1_2_7_33_1","doi-asserted-by":"publisher","DOI":"10.1002\/jbmr.354"},{"key":"e_1_2_7_34_1","doi-asserted-by":"publisher","DOI":"10.1038\/bonekey.2013.215"},{"key":"e_1_2_7_35_1","doi-asserted-by":"publisher","DOI":"10.1097\/BOT.0b013e3181ed147b"},{"key":"e_1_2_7_36_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.181.2.1232"},{"key":"e_1_2_7_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajpath.2014.08.017"},{"key":"e_1_2_7_38_1","doi-asserted-by":"publisher","DOI":"10.1002\/stem.1040"},{"key":"e_1_2_7_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2014.04.050"},{"key":"e_1_2_7_40_1","doi-asserted-by":"publisher","DOI":"10.1002\/term.535"},{"key":"e_1_2_7_41_1","doi-asserted-by":"publisher","DOI":"10.2106\/JBJS.I.00097"},{"key":"e_1_2_7_42_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1445-2197.2008.04803.x"},{"key":"e_1_2_7_43_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1432-0436.2001.680412.x"},{"key":"e_1_2_7_44_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0056641"}],"container-title":["The Journal of Pathology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fpath.4519","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fpath.4519","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/pathsocjournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/path.4519","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,20]],"date-time":"2025-10-20T13:27:59Z","timestamp":1760966879000},"score":1,"resource":{"primary":{"URL":"https:\/\/pathsocjournals.onlinelibrary.wiley.com\/doi\/10.1002\/path.4519"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,3,26]]},"references-count":43,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2015,6]]}},"alternative-id":["10.1002\/path.4519"],"URL":"https:\/\/doi.org\/10.1002\/path.4519","archive":["Portico"],"relation":{},"ISSN":["0022-3417","1096-9896"],"issn-type":[{"value":"0022-3417","type":"print"},{"value":"1096-9896","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,3,26]]},"assertion":[{"value":"2015-01-08","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2015-02-19","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2015-03-26","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}