{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,29]],"date-time":"2026-01-29T12:03:03Z","timestamp":1769688183997,"version":"3.49.0"},"reference-count":44,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2025,12,18]],"date-time":"2025-12-18T00:00:00Z","timestamp":1766016000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2025,12,18]],"date-time":"2025-12-18T00:00:00Z","timestamp":1766016000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100000069","name":"National Institute of Arthritis and Musculoskeletal and Skin Diseases","doi-asserted-by":"publisher","award":["F31 AR082294"],"award-info":[{"award-number":["F31 AR082294"]}],"id":[{"id":"10.13039\/100000069","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000069","name":"National Institute of Arthritis and Musculoskeletal and Skin Diseases","doi-asserted-by":"publisher","award":["R01AR075730"],"award-info":[{"award-number":["R01AR075730"]}],"id":[{"id":"10.13039\/100000069","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000069","name":"National Institute of Arthritis and Musculoskeletal and Skin Diseases","doi-asserted-by":"publisher","award":["R01AR083421"],"award-info":[{"award-number":["R01AR083421"]}],"id":[{"id":"10.13039\/100000069","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000069","name":"National Institute of Arthritis and Musculoskeletal and Skin Diseases","doi-asserted-by":"publisher","award":["2018\/23676\u20103"],"award-info":[{"award-number":["2018\/23676\u20103"]}],"id":[{"id":"10.13039\/100000069","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal Orthopaedic Research"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>MicroRNAs are small non\u2010coding RNAs that regulate cellular pathways by targeting multiple mRNAs, playing critical roles in skeletal development and homeostasis. Our previous miRNA profiling studies identified higher levels of miR\u2010127\u20103p in the hypertrophic zone of developing human growth plates while another group found this miRNA to be more highly expressed in murine hindlimb cartilage compared to calvarial bone. Other published work revealed elevated circulating miR\u2010127\u20103p levels in osteoporotic patients and in long bones of ovariectomized mice. Collectively, these findings suggest a role for miR\u2010127\u20103p in regulating bone formation. To fill a knowledge gap, we designed a study to determine the function of miR\u2010127\u20103p in regulating osteogenic differentiation of human bone marrow\u2010derived mesenchymal stromal cells (hBMSCs). While inhibition of miR\u2010127\u20103p had no effect, mimic overexpression robustly inhibited in vitro osteogenesis. Bulk RNA\u2010sequencing showed a number of cellular pathways affected, including suppression of proliferation\u2010related pathways, which was confirmed by decreased BrdU incorporation. To assess the translational potential of the bone suppressing function of this miRNA, we utilized a pre\u2010clinical mouse model of trauma\u2010induced heterotopic ossification involving Achilles tendon transection. Local delivery of miR\u2010127\u20103p mimics via peptide\u2010based nanoparticle technology significantly reduced ectopic bone formation at the proximal site of the transected tendon. These studies demonstrate that approaches to overexpress miR\u2010127\u20103p and induce bone suppressing activity may be of therapeutic value as a means to treat many forms of heterotopic ossification.<\/jats:p>","DOI":"10.1002\/jor.70123","type":"journal-article","created":{"date-parts":[[2025,12,18]],"date-time":"2025-12-18T08:39:58Z","timestamp":1766047198000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["MicroRNA\u2010127\u20103p Inhibits In Vitro Osteogenesis and Dampens Trauma\u2010Induced Heterotopic Ossification In Vivo"],"prefix":"10.1002","volume":"44","author":[{"given":"Victor Gustavo Balera","family":"Brito","sequence":"first","affiliation":[{"name":"Department of Orthopaedic Surgery Washington University School of Medicine St. Louis Missouri USA"},{"name":"Department of Basic Sciences, Multicenter Graduate Program in Physiological Sciences Brazilian Society of Physiology Ara\u00e7atuba S\u00e3o Paulo Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Austin","family":"Bell\u2010Hensley","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering Washington University School of Medicine St. Louis Missouri USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hongjun","family":"Zheng","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery Washington University School of Medicine St. Louis Missouri USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jin","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery Washington University School of Medicine St. Louis Missouri USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Arya","family":"Narayan","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery Washington University School of Medicine St. Louis Missouri USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0805-1120","authenticated-orcid":false,"given":"Sandra Helena Penha","family":"Oliveria","sequence":"additional","affiliation":[{"name":"Department of Basic Sciences, Multicenter Graduate Program in Physiological Sciences Brazilian Society of Physiology Ara\u00e7atuba S\u00e3o Paulo Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hua","family":"Pan","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering Washington University School of Medicine St. Louis Missouri USA"},{"name":"Department of Medicine Washington University School of Medicine St. Louis Missouri USA"},{"name":"Department of Pathology and Immunology Washington University School of Medicine St. Louis Missouri USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Audrey","family":"McAlinden","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery Washington University School of Medicine St. Louis Missouri USA"},{"name":"Department of Cell Biology &amp; Physiology Washington University School of Medicine St. Louis Missouri USA"},{"name":"Shriners Hospital for Children\u2010St Louis  Missouri USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,12,18]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2009.01.002"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/jor.23822"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bone.2020.115760"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrendo.2011.234"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccr.2006.04.020"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0075012"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0707900105"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.3892\/etm.2017.4711"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.reth.2021.09.004"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2018.12.116"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/jbmr.2060"},{"key":"e_1_2_9_13_1","first-page":"1383","article-title":"Circulating MicroRNAs, miR\u201010b\u20105p, miR\u2010328\u20103p, miR\u2010100 and let\u20107, Are Associated With Osteoblast Differentiation in Osteoporosis","volume":"11","author":"Chen R.","year":"2018","journal-title":"International Journal of Clinical and Experimental Pathology"},{"issue":"102","key":"e_1_2_9_14_1","article-title":"Direct Mouse Trauma\/Burn Model of Heterotopic Ossification","author":"Peterson J. R.","year":"2015","journal-title":"Journal of Visualized Experiments: JoVE"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.2019"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1006\/meth.2001.1262"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2013.01.037"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-019-41122-3"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1608245113"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.05005"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.3892\/or.2014.3055"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/jbm4.10071"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm1716"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI96221"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2024.1451695"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1530\/JOE-25-0032"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-33938-x"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1093\/jbmrpl\/ziad014"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1248\/bpb.32.1166"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2021.740203"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13238-017-0377-7"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biocel.2013.05.017"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1086\/324023"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.33240"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-019-50336-4"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells11101609"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.reth.2024.03.025"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1210\/jcem.83.3.4674"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.mp.4000563"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10038-003-0090-7"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.1021\/nn403311c"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00167-021-06767-6"},{"key":"e_1_2_9_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mtbio.2025.101458"},{"key":"e_1_2_9_44_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.85873"},{"key":"e_1_2_9_45_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2022.11.007"}],"container-title":["Journal of Orthopaedic Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jor.70123","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/jor.70123","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jor.70123","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,29]],"date-time":"2026-01-29T00:56:43Z","timestamp":1769648203000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/jor.70123"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12,18]]},"references-count":44,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2026,1]]}},"alternative-id":["10.1002\/jor.70123"],"URL":"https:\/\/doi.org\/10.1002\/jor.70123","archive":["Portico"],"relation":{},"ISSN":["0736-0266","1554-527X"],"issn-type":[{"value":"0736-0266","type":"print"},{"value":"1554-527X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,12,18]]},"assertion":[{"value":"2025-10-08","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-12-10","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-12-18","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70123"}}