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dc.contributor.authorPrasadam, Indira
dc.contributor.authorBatra, Jyotsna
dc.contributor.authorPerry, Samuel
dc.contributor.authorGu, Wenyi
dc.contributor.authorCrawford, Ross
dc.contributor.authorXiao, Yin
dc.date.accessioned2018-03-05T02:53:35Z
dc.date.available2018-03-05T02:53:35Z
dc.date.issued2016
dc.identifier.issn0171-967X
dc.identifier.doi10.1007/s00223-016-0125-7
dc.identifier.urihttp://hdl.handle.net/10072/370488
dc.description.abstractThis study aimed to identify the microRNAs associated with sclerotic status of subchondral bone in the pathogenesis of osteoarthritis (OA). Total RNA was extracted from non-sclerotic and sclerotic OA subchondral bone from patients undergoing knee replacement surgeries. miRCURY™ LNA miRNA chip and qRT-PCR were used to profile and validate differential microRNA expression. In addition, we further confirmed profiles of altered miRNAs in an OA rat meniscectomy animal model and their putative targets of the miRNAs were predicted using ingenuity (IPA) software. Finally, five short-listed miRNAs were reactivated by transient in vitro overexpression (miRNA mimics) in subchondral bone osteoblasts and their phenotypes were assessed. Functional screening identified 30 differentiated miRNAs in sclerotic subchondral bone compared to non-sclerotic bone of OA patients. Data integration resulted in confirmation of the eight miRNAs, with aberrant expression in independent human OA bone sample set. In silico analysis (IPA) identified 732 mRNA transcripts as putative targets of the eight altered miRNAs, of which twenty genes were validated to be differentially expressed in sclerotic compared to non-sclerotic bone samples. Out of eight dysregulated miRNA’s, five of them showed consistent time-dependent downregulation in a rat OA model. Furthermore, synthetic miR-199a-3p, miR-199a-5p, miR-590-5p, and miR-211-5p mimics rescued the abnormal osteoarthritic subchondral bone osteoblast gene expression and mineralization. We have identified four novel miRNAs that play important roles in subchondral bone pathogenesis in OA. Additional studies are required to develop these miRNAs into therapeutic modalities for OA.
dc.description.peerreviewedYes
dc.languageEnglish
dc.language.isoeng
dc.publisherSpringer
dc.relation.ispartofpagefrom43
dc.relation.ispartofpageto55
dc.relation.ispartofissue1
dc.relation.ispartofjournalCalcified Tissue International
dc.relation.ispartofvolume99
dc.subject.fieldofresearchGenetic Immunology
dc.subject.fieldofresearchBiochemistry and Cell Biology
dc.subject.fieldofresearchBiomedical Engineering
dc.subject.fieldofresearchClinical Sciences
dc.subject.fieldofresearchcode060406
dc.subject.fieldofresearchcode0601
dc.subject.fieldofresearchcode0903
dc.subject.fieldofresearchcode1103
dc.titleSystematic Identification, Characterization and Target Gene Analysis of microRNAs Involved in Osteoarthritis Subchondral Bone Pathogenesis
dc.typeJournal article
dc.type.descriptionC1 - Articles
dc.type.codeC - Journal Articles
gro.hasfulltextNo Full Text
gro.griffith.authorPerry, Samuel


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