{"@context":{"@vocab":"https://cir.nii.ac.jp/schema/1.0/","rdfs":"http://www.w3.org/2000/01/rdf-schema#","dc":"http://purl.org/dc/elements/1.1/","dcterms":"http://purl.org/dc/terms/","foaf":"http://xmlns.com/foaf/0.1/","prism":"http://prismstandard.org/namespaces/basic/2.0/","cinii":"http://ci.nii.ac.jp/ns/1.0/","datacite":"https://schema.datacite.org/meta/kernel-4/","ndl":"http://ndl.go.jp/dcndl/terms/","jpcoar":"https://github.com/JPCOAR/schema/blob/master/2.0/"},"@id":"https://cir.nii.ac.jp/crid/1361418518924230656.json","@type":"Article","productIdentifier":[{"identifier":{"@type":"DOI","@value":"10.1002/jbmr.377"}},{"identifier":{"@type":"URI","@value":"https://api.wiley.com/onlinelibrary/tdm/v1/articles/10.1002%2Fjbmr.377"}},{"identifier":{"@type":"URI","@value":"https://academic.oup.com/jbmr/article-pdf/26/8/1953/56557755/377_ftp.pdf"}}],"dc:title":[{"@value":"Effects of miR-335-5p in modulating osteogenic differentiation by specifically downregulating Wnt antagonist DKK1"}],"description":[{"type":"abstract","notation":[{"@value":"<jats:title>Abstract</jats:title>\n               <jats:p>Dickkopf-related protein 1 (DKK1) is essential to maintain skeletal homeostasis as an inhibitor of Wnt signaling and osteogenic differentiation. The purpose of this study was to investigate the molecular mechanisms underlying the developmental stage–specific regulation of the DKK1 protein level. We performed a series of studies including luciferase reporter assays, micro-RNA microarray, site-specific mutations, and gain- and loss-of-function analyses. We found that the DKK1 protein level was regulated via DKK1 3' UTR by miRNA control, which was restricted to osteoblast-lineage cells. As a result of decreased DKK1 protein level by miR-335-5p, Wnt signaling was enhanced, as indicated by elevated GSK-3β phosphorylation and increased β-catenin transcriptional activity. The effects of miR-335-5p were reversed by anti-miR-335-5p treatment, which downregulated endogenous miR-335-5p. In vivo studies showed high expression levels of miR-335-5p in osteoblasts and hypertrophic chondrocytes of mouse embryos, indicating a pivotal role of miR-335-5p in regulating bone development. In conclusion, miR-335-5p activates Wnt signaling and promotes osteogenic differentiation by downregulating DKK1. This cell- and development-specific regulation is essential and mandatory for the initiation and progression of osteogenic differentiation. miR-335-5p proves to be a potential and useful targeting molecule for promoting bone formation and regeneration. © 2011 American Society for Bone and Mineral Research</jats:p>"}]}],"creator":[{"@id":"https://cir.nii.ac.jp/crid/1381418518924230659","@type":"Researcher","foaf:name":[{"@value":"Jin Zhang"}],"jpcoar:affiliationName":[{"@value":"Department of Periodontology, School of Dentistry, Shandong University, Shandong, China"},{"@value":"Division of Oral Biology, Tufts University School of Dental Medicine, Boston, MA, USA"}]},{"@id":"https://cir.nii.ac.jp/crid/1381418518924230658","@type":"Researcher","foaf:name":[{"@value":"Qisheng Tu"}],"jpcoar:affiliationName":[{"@value":"Division of Oral Biology, Tufts University School of Dental Medicine, Boston, MA, USA"}]},{"@id":"https://cir.nii.ac.jp/crid/1381418518924230657","@type":"Researcher","foaf:name":[{"@value":"Lynda F Bonewald"}],"jpcoar:affiliationName":[{"@value":"School of Dentistry, University of Missouri–Kansas City, Kansas City, MO, USA"}]},{"@id":"https://cir.nii.ac.jp/crid/1381418518924230661","@type":"Researcher","foaf:name":[{"@value":"Xi He"}],"jpcoar:affiliationName":[{"@value":"Children's Hospital, Harvard Medical School, Boston, MA, USA"}]},{"@id":"https://cir.nii.ac.jp/crid/1381418518924230656","@type":"Researcher","foaf:name":[{"@value":"Gary Stein"}],"jpcoar:affiliationName":[{"@value":"Department of Cell Biology, University of Massachusetts Medical School, Worcester, MA, USA"}]},{"@id":"https://cir.nii.ac.jp/crid/1381418518924230660","@type":"Researcher","foaf:name":[{"@value":"Jane Lian"}],"jpcoar:affiliationName":[{"@value":"Department of Cell Biology, University of Massachusetts Medical School, Worcester, MA, USA"}]},{"@id":"https://cir.nii.ac.jp/crid/1381418518924230662","@type":"Researcher","foaf:name":[{"@value":"Jake Chen"}],"jpcoar:affiliationName":[{"@value":"Department of Anatomy and Cell Biology, Tufts University School of Medicine, Boston, MA, USA"},{"@value":"Division of Oral Biology, Tufts University School of Dental Medicine, Boston, MA, USA"}]}],"publication":{"publicationIdentifier":[{"@type":"PISSN","@value":"08840431"},{"@type":"EISSN","@value":"15234681"}],"prism:publicationName":[{"@value":"Journal of Bone and Mineral Research"}],"dc:publisher":[{"@value":"Oxford University Press (OUP)"}],"prism:publicationDate":"2011-02-23","prism:volume":"26","prism:number":"8","prism:startingPage":"1953","prism:endingPage":"1963"},"reviewed":"false","dc:rights":["https://academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model"],"url":[{"@id":"https://api.wiley.com/onlinelibrary/tdm/v1/articles/10.1002%2Fjbmr.377"},{"@id":"https://academic.oup.com/jbmr/article-pdf/26/8/1953/56557755/377_ftp.pdf"}],"createdAt":"2011-02-26","modifiedAt":"2024-03-13","relatedProduct":[{"@id":"https://cir.nii.ac.jp/crid/1390282680522398592","@type":"Article","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@language":"en","@value":"Circular RNAs and hereditary bone diseases"}]}],"dataSourceIdentifier":[{"@type":"CROSSREF","@value":"10.1002/jbmr.377"},{"@type":"CROSSREF","@value":"10.5582/irdr.2018.01013_references_DOI_2LrqbrqdqHtYGkoj65LwyJftq68"}]}