{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,21]],"date-time":"2026-02-21T19:47:33Z","timestamp":1771703253538,"version":"3.50.1"},"reference-count":36,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2020,4,13]],"date-time":"2020-04-13T00:00:00Z","timestamp":1586736000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01AR073181, R01AR056837"],"award-info":[{"award-number":["R01AR073181, R01AR056837"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Osteochondromas are cartilage-capped growths located proximate to the physis that can cause skeletal deformities, pain, limited motion, and neurovascular impingement. Previous studies have demonstrated retinoic acid receptor gamma (RAR\u03b3) agonists to inhibit ectopic endochondral ossification, therefore we hypothesize that RAR\u03b3 agonists can target on established osteochondromas. The purpose of this study was to examine the action of RAR\u03b3 agonist in human osteochondromas. Osteochondroma specimens were obtained during surgery, subjected to explant culture and were treated with RAR\u03b3 agonists or vehicles. Gene expression analysis confirmed the up-regulation of RAR\u03b3 target genes in the explants treated with NRX 204647 and Palovarotene and revealed strong inhibition of cartilage matrix and increased extracellular matrix proteases gene expression. In addition, immunohistochemical staining for the neoepitope of protease-cleaved aggrecan indicated that RAR\u03b3 agonist treatment stimulated cartilage matrix degradation. Interestingly, cell survival studies demonstrated that RAR\u03b3 agonist treatment stimulated cell death. Moreover, RNA sequencing analysis indicates changes in multiple molecular pathways due to RAR\u03b3 agonists treatment, showing similarly to human growth plate chondrocytes. Together, these findings suggest that RAR\u03b3 agonist may exert anti-tumor function on osteochondromas by inhibiting matrix synthesis, promoting cartilage matrix degradation and stimulating cell death.<\/jats:p>","DOI":"10.3390\/ijms21082686","type":"journal-article","created":{"date-parts":[[2020,4,13]],"date-time":"2020-04-13T10:41:52Z","timestamp":1586774512000},"page":"2686","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Understanding the Action of RAR\u03b3 Agonists on Human Osteochondroma Explants"],"prefix":"10.3390","volume":"21","author":[{"given":"Sonia A.","family":"Garcia","sequence":"first","affiliation":[{"name":"Department of Orthopaedics,  University of Maryland School of Medicine, 20 Penn Street, HSFII, Baltimore, MD 21201, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hongying","family":"Tian","sequence":"additional","affiliation":[{"name":"Department of Orthopaedics,  University of Maryland School of Medicine, 20 Penn Street, HSFII, Baltimore, MD 21201, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuka","family":"Imamura-Kawasawa","sequence":"additional","affiliation":[{"name":"Departments of Pharmacology and Biochemistry and Molecular Biology, Institute for Personalized Medicine, Pennsylvania State University College of Medicine, Hershey, PA 17033, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5706-537X","authenticated-orcid":false,"given":"Aidan","family":"Fisher","sequence":"additional","affiliation":[{"name":"Department of Orthopaedics,  University of Maryland School of Medicine, 20 Penn Street, HSFII, Baltimore, MD 21201, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ashley","family":"Cellini","sequence":"additional","affiliation":[{"name":"Department of Orthopaedics,  University of Maryland School of Medicine, 20 Penn Street, HSFII, Baltimore, MD 21201, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9424-6404","authenticated-orcid":false,"given":"Casey","family":"Codd","sequence":"additional","affiliation":[{"name":"Department of Orthopaedics,  University of Maryland School of Medicine, 20 Penn Street, HSFII, Baltimore, MD 21201, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John E.","family":"Herzenberg","sequence":"additional","affiliation":[{"name":"Department of Orthopaedics,  University of Maryland School of Medicine, 20 Penn Street, HSFII, Baltimore, MD 21201, USA"},{"name":"Pediatric Orthopaedics, Sinai Hospital, Baltimore, MD 21215, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joshua M.","family":"Abzug","sequence":"additional","affiliation":[{"name":"Department of Orthopaedics,  University of Maryland School of Medicine, 20 Penn Street, HSFII, Baltimore, MD 21201, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vincent","family":"Ng","sequence":"additional","affiliation":[{"name":"Department of Orthopaedics,  University of Maryland School of Medicine, 20 Penn Street, HSFII, Baltimore, MD 21201, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masahiro","family":"Iwamoto","sequence":"additional","affiliation":[{"name":"Department of Orthopaedics,  University of Maryland School of Medicine, 20 Penn Street, HSFII, Baltimore, MD 21201, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Motomi","family":"Enomoto-Iwamoto","sequence":"additional","affiliation":[{"name":"Department of Orthopaedics,  University of Maryland School of Medicine, 20 Penn Street, HSFII, Baltimore, MD 21201, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2020,4,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"555","DOI":"10.1016\/j.rbo.2013.10.024","article-title":"Osteochondroma: Ignore or investigate?","volume":"49","year":"2014","journal-title":"Rev. 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