{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T14:33:54Z","timestamp":1786113234570,"version":"build-2736575974"},"reference-count":79,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"861","funder":[{"DOI":"10.13039\/100000005","name":"U.S. Department of Defense","doi-asserted-by":"publisher","award":["P01 AG066603"],"award-info":[{"award-number":["P01 AG066603"]}],"id":[{"id":"10.13039\/100000005","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000005","name":"U.S. Department of Defense","doi-asserted-by":"publisher","award":["R01 AR079171"],"award-info":[{"award-number":["R01 AR079171"]}],"id":[{"id":"10.13039\/100000005","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000005","name":"U.S. Department of Defense","doi-asserted-by":"publisher","award":["R01 AR079171-07S1"],"award-info":[{"award-number":["R01 AR079171-07S1"]}],"id":[{"id":"10.13039\/100000005","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000005","name":"U.S. Department of Defense","doi-asserted-by":"publisher","award":["R21AR078919"],"award-info":[{"award-number":["R21AR078919"]}],"id":[{"id":"10.13039\/100000005","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000005","name":"U.S. Department of Defense","doi-asserted-by":"publisher","award":["R21AR083544"],"award-info":[{"award-number":["R21AR083544"]}],"id":[{"id":"10.13039\/100000005","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000005","name":"U.S. Department of Defense","doi-asserted-by":"publisher","award":["R01 DE031488"],"award-info":[{"award-number":["R01 DE031488"]}],"id":[{"id":"10.13039\/100000005","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000005","name":"U.S. Department of Defense","doi-asserted-by":"publisher","award":["R01 DE031028"],"award-info":[{"award-number":["R01 DE031028"]}],"id":[{"id":"10.13039\/100000005","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000005","name":"U.S. Department of Defense","doi-asserted-by":"publisher","award":["22-26743"],"award-info":[{"award-number":["22-26743"]}],"id":[{"id":"10.13039\/100000005","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000005","name":"U.S. Department of Defense","doi-asserted-by":"publisher","award":["DBG-23-1155131-01-IBCD"],"award-info":[{"award-number":["DBG-23-1155131-01-IBCD"]}],"id":[{"id":"10.13039\/100000005","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000005","name":"U.S. Department of Defense","doi-asserted-by":"publisher","award":["2021-MSCRFD-5641"],"award-info":[{"award-number":["2021-MSCRFD-5641"]}],"id":[{"id":"10.13039\/100000005","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000005","name":"U.S. Department of Defense","doi-asserted-by":"publisher","award":["USAMRAA HT9425-24-1-0051"],"award-info":[{"award-number":["USAMRAA HT9425-24-1-0051"]}],"id":[{"id":"10.13039\/100000005","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":[[2026,8,5]]},"abstract":"<jats:p>Somatosensory neurons detect a diverse repertoire of stimuli, including in skeletal tissues, in which sensations of pain, pressure, and position are transmitted. Trauma to the physis often leads to pathologic \u201cbony bar\u201d formation, impeding normal growth of the skeleton. The role of somatosensory nerves in detecting and, in turn, regulating physis injury is unknown. Here, we observed prominent sensory nerve growth within the injured physis in mouse and human tissues corresponding to domains of nerve growth factor (NGF) expression. Two independent methods to inhibit tropomyosin receptor kinase A (TrkA) signaling reduced nerve sprouting and attenuated pathologic bony bar formation, whereas conversely sensory neural conditioned medium\u2013treated organ cultures demonstrated the opposing effects. Somatosensory nerve retrograde tracing and single-cell RNA sequencing (scRNA-seq) identified a sensorineural transcriptome evoked by physis injury in mice. Corresponding scRNA-seq of injured mouse growth plates implicated pleiotrophin (PTN) signaling in pathologic growth plate ossification, a finding confirmed by ex vivo organ culture and in vivo knockout in sensory ganglia. Last, FDA-approved long-acting bupivacaine prevented pathological innervation and ossification of the growth plate after injury. These findings suggest that targeting somatosensory nerves could offer previously unrecognized strategies to treat pain and prevent pathologic ossification to optimize patient outcomes after growth plate injury.<\/jats:p>","DOI":"10.1126\/scitranslmed.adv2412","type":"journal-article","created":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T17:58:14Z","timestamp":1785952694000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":0,"title":["Somatosensory nerves drive pathologic bony bar formation after physis injury through pleiotrophin signaling in mouse models"],"prefix":"10.1126","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9276-9129","authenticated-orcid":true,"given":"Zhao","family":"Li","sequence":"first","affiliation":[{"name":"Department of Pathology, Johns Hopkins University, Baltimore, MD 21205, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6417-0664","authenticated-orcid":true,"given":"Xin","family":"Xing","sequence":"additional","affiliation":[{"name":"Department of Pathology, Johns Hopkins University, Baltimore, MD 21205, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-9064-5763","authenticated-orcid":true,"given":"Beicheng","family":"Du","sequence":"additional","affiliation":[{"name":"Department of Pathology, Johns Hopkins University, Baltimore, MD 21205, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4537-8800","authenticated-orcid":true,"given":"Myles","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Pathology, Johns Hopkins University, Baltimore, MD 21205, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunbao","family":"Rao","sequence":"additional","affiliation":[{"name":"Department of Pathology, Johns Hopkins University, Baltimore, MD 21205, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qizhi","family":"Qin","sequence":"additional","affiliation":[{"name":"Department of Pathology, Johns Hopkins University, Baltimore, MD 21205, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-1262-2039","authenticated-orcid":true,"given":"Austin Z.","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Pathology, Johns Hopkins University, Baltimore, MD 21205, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4086-9603","authenticated-orcid":true,"given":"Sowmya","family":"Ramesh","sequence":"additional","affiliation":[{"name":"Department of Pathology, Johns Hopkins University, Baltimore, MD 21205, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-1579-1056","authenticated-orcid":true,"given":"Mary","family":"Archer","sequence":"additional","affiliation":[{"name":"Department of Pathology, Johns Hopkins University, Baltimore, MD 21205, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-3492-4305","authenticated-orcid":true,"given":"Manyu","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Pathology, Johns Hopkins University, Baltimore, MD 21205, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3973-7117","authenticated-orcid":true,"given":"Neelima","family":"Thottappillil","sequence":"additional","affiliation":[{"name":"Department of Pathology, Johns Hopkins University, Baltimore, MD 21205, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0009-2905","authenticated-orcid":true,"given":"JiHye","family":"Yea","sequence":"additional","affiliation":[{"name":"Department of Pathology, Johns Hopkins University, Baltimore, MD 21205, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1334-7287","authenticated-orcid":true,"given":"Ziyi","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Pathology, Johns Hopkins University, Baltimore, MD 21205, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8645-2363","authenticated-orcid":true,"given":"Erin","family":"Honcharuk","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery, Johns Hopkins University, Baltimore, MD 21205, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2002-622X","authenticated-orcid":true,"given":"Aaron W.","family":"James","sequence":"additional","affiliation":[{"name":"Department of Pathology, Johns Hopkins University, Baltimore, MD 21205, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"221","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00441-001-0477-8"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2018.10.024"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jdermsci.2014.02.001"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2024.03.008"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41577-020-0387-1"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12964-020-00656-0"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature01657"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.3382\/ps.0701806"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1097\/01241398-199011000-00002"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1097\/01241398-198709000-00003"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bone.2011.07.024"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI128428"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41413-022-00216-x"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2020.107696"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1038\/s12276-022-00899-6"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-25143-z"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2103087118"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.ade4619"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1093\/stcltm\/szac073"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1701054114"},{"key":"e_1_3_2_22_2","article-title":"Local changes to the distal femoral growth plate following injury in mice","volume":"139","author":"Drenkard L. M. M.","year":"2017","unstructured":"L. M. M. Drenkard, M. E. Kupratis, K. Li, L. C. Gerstenfeld, E. F. Morgan, Local changes to the distal femoral growth plate following injury in mice. J. Biomech. Eng. 139, 071010 (2017).","journal-title":"J. Biomech. Eng."},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1038\/nn2034"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1002\/cne.22629"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(02)00757-2"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1096\/fj.201903236R"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2016.08.002"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2005.03.009"},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmcl.2003.12.002"},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.1038\/nn.4593"},{"key":"e_1_3_2_31_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-019-1900-1"},{"key":"e_1_3_2_32_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2024.02.006"},{"key":"e_1_3_2_33_2","doi-asserted-by":"publisher","DOI":"10.1038\/368246a0"},{"key":"e_1_3_2_34_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2011.01.039"},{"key":"e_1_3_2_35_2","doi-asserted-by":"publisher","DOI":"10.1177\/1744806917745465"},{"key":"e_1_3_2_36_2","doi-asserted-by":"publisher","DOI":"10.1038\/pr.2014.208"},{"key":"e_1_3_2_37_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0062994"},{"key":"e_1_3_2_38_2","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.182524"},{"key":"e_1_3_2_39_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2019152118"},{"key":"e_1_3_2_40_2","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.81656"},{"key":"e_1_3_2_41_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41413-025-00407-2"},{"key":"e_1_3_2_42_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.aax0249"},{"key":"e_1_3_2_43_2","doi-asserted-by":"publisher","DOI":"10.1387\/ijdb.210122ep"},{"key":"e_1_3_2_44_2","doi-asserted-by":"publisher","DOI":"10.1016\/bs.acc.2020.02.003"},{"key":"e_1_3_2_45_2","doi-asserted-by":"publisher","DOI":"10.1007\/s004020000246"},{"key":"e_1_3_2_46_2","doi-asserted-by":"publisher","DOI":"10.1016\/0266-7681_87_90046-5"},{"key":"e_1_3_2_47_2","doi-asserted-by":"publisher","DOI":"10.1097\/AAP.0b013e3181e82df0"},{"key":"e_1_3_2_48_2","unstructured":"Pacira BioSciences Inc. Exparel (2025); https:\/\/pacira.com\/therapies\/exparel\/."},{"key":"e_1_3_2_49_2","doi-asserted-by":"publisher","DOI":"10.5435\/00124635-200501000-00007"},{"key":"e_1_3_2_50_2","doi-asserted-by":"publisher","DOI":"10.2214\/ajr.178.4.1780967"},{"key":"e_1_3_2_51_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.injury.2014.10.013"},{"key":"e_1_3_2_52_2","doi-asserted-by":"publisher","DOI":"10.1080\/03008207.2020.1779238"},{"key":"e_1_3_2_53_2","doi-asserted-by":"publisher","DOI":"10.1111\/jre.13073"},{"key":"e_1_3_2_54_2","doi-asserted-by":"publisher","DOI":"10.1093\/oxfordjournals.jbchem.a003178"},{"key":"e_1_3_2_55_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.actbio.2018.07.048"},{"key":"e_1_3_2_56_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10143-009-0202-8"},{"key":"e_1_3_2_57_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1460-9568.2003.02661.x"},{"key":"e_1_3_2_58_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0603243104"},{"key":"e_1_3_2_59_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00221-019-05644-6"},{"key":"e_1_3_2_60_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2010.08.029"},{"key":"e_1_3_2_61_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbcan.2016.09.007"},{"key":"e_1_3_2_62_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10456-020-09733-x"},{"key":"e_1_3_2_63_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1206879"},{"key":"e_1_3_2_64_2","doi-asserted-by":"publisher","DOI":"10.1002\/dvdy.20512"},{"key":"e_1_3_2_65_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.20110"},{"key":"e_1_3_2_66_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.24860"},{"key":"e_1_3_2_67_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.matbio.2016.01.008"},{"key":"e_1_3_2_68_2","doi-asserted-by":"publisher","DOI":"10.1038\/nn1193"},{"key":"e_1_3_2_69_2","doi-asserted-by":"publisher","DOI":"10.4103\/1673-5374.335144"},{"key":"e_1_3_2_70_2","first-page":"72","article-title":"Chondroitin sulfate proteoglycans from salmon nasal cartilage inhibit angiogenesis","volume":"9","author":"Kobayashi T.","year":"2017","unstructured":"T. Kobayashi, I. Kakizaki, H. Nozaka, T. Nakamura, Chondroitin sulfate proteoglycans from salmon nasal cartilage inhibit angiogenesis. Biochem. Biophys. Rep. 9, 72\u201378 (2017).","journal-title":"Biochem. Biophys. Rep."},{"key":"e_1_3_2_71_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.semcdb.2011.09.010"},{"key":"e_1_3_2_72_2","doi-asserted-by":"publisher","DOI":"10.1530\/JME-14-0062"},{"key":"e_1_3_2_73_2","doi-asserted-by":"publisher","DOI":"10.1097\/BPO.0000000000001093"},{"key":"e_1_3_2_74_2","doi-asserted-by":"publisher","DOI":"10.1097\/BPO.0b013e3181a6bfe8"},{"key":"e_1_3_2_75_2","doi-asserted-by":"publisher","DOI":"10.52965\/001c.32319"},{"key":"e_1_3_2_76_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2018.07.003"},{"key":"e_1_3_2_77_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI96060"},{"key":"e_1_3_2_78_2","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.abj5435"},{"key":"e_1_3_2_79_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bja.2020.04.091"},{"key":"e_1_3_2_80_2","doi-asserted-by":"publisher","DOI":"10.1093\/stmcls\/sxag014"}],"container-title":["Science Translational Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.science.org\/doi\/pdf\/10.1126\/scitranslmed.adv2412","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T17:58:18Z","timestamp":1785952698000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.science.org\/doi\/10.1126\/scitranslmed.adv2412"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,5]]},"references-count":79,"journal-issue":{"issue":"861","published-print":{"date-parts":[[2026,8,5]]}},"alternative-id":["10.1126\/scitranslmed.adv2412"],"URL":"https:\/\/doi.org\/10.1126\/scitranslmed.adv2412","relation":{},"ISSN":["1946-6234","1946-6242"],"issn-type":[{"value":"1946-6234","type":"print"},{"value":"1946-6242","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,5]]},"assertion":[{"value":"2025-01-15","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-12-15","order":1,"name":"revised","label":"Revised","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-07-15","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-08-05","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"eadv2412"}}