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dc.contributor.authorGarcia, S.A.
dc.contributor.authorTian, H.
dc.contributor.authorFisher, A.
dc.contributor.authorCellini, A.
dc.contributor.authorCodd, C.
dc.contributor.authorHerzenberg, J.E.
dc.contributor.authorAbzug, J.M.
dc.contributor.authorNg, V.
dc.contributor.authorIwamoto, M.
dc.contributor.authorEnomoto-Iwamoto, M.
dc.date.accessioned2020-04-28T20:12:23Z
dc.date.available2020-04-28T20:12:23Z
dc.date.issued2020
dc.identifier.urihttps://www.scopus.com/inward/record.uri?eid=2-s2.0-85083477844&doi=10.3390%2fijms21082686&partnerID=40&md5=eaf91815718355a785780d9f740eb6ec
dc.identifier.urihttp://hdl.handle.net/10713/12669
dc.description.abstractOsteochondromas 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 (RARγ) agonists to inhibit ectopic endochondral ossification, therefore we hypothesize that RARγ agonists can target on established osteochondromas. The purpose of this study was to examine the action of RARγ agonist in human osteochondromas. Osteochondroma specimens were obtained during surgery, subjected to explant culture and were treated with RARγ agonists or vehicles. Gene expression analysis confirmed the up-regulation of RARγ 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 RARγ agonist treatment stimulated cartilage matrix degradation. Interestingly, cell survival studies demonstrated that RARγ agonist treatment stimulated cell death. Moreover, RNA sequencing analysis indicates changes in multiple molecular pathways due to RARγ agonists treatment, showing similarly to human growth plate chondrocytes. Together, these findings suggest that RARγ agonist may exert anti-tumor function on osteochondromas by inhibiting matrix synthesis, promoting cartilage matrix degradation and stimulating cell death.en_US
dc.description.urihttps://doi.org/10.3390/ijms21082686en_US
dc.language.isoen_USen_US
dc.publisherMDPI AGen_US
dc.relation.ispartofInternational journal of molecular sciences
dc.subjectgrowth plateen_US
dc.subjectosteochondromaen_US
dc.subjectretinoic acid nuclear receptoren_US
dc.subjecttranscriptome analysisen_US
dc.subjectRARγ agonistsen_US
dc.titleUnderstanding the Action of RARγ Agonists on Human Osteochondroma Explantsen_US
dc.typeArticleen_US
dc.identifier.doi10.3390/ijms21082686
dc.identifier.pmid32294904


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