Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
24
pubmed:dateCreated
2011-6-15
pubmed:abstractText
Lineage progression in osteoblasts and chondrocytes is stringently controlled by the cell-fate-determining transcription factor Runx2. In this study, we directly addressed whether microRNAs (miRNAs) can control the osteogenic activity of Runx2 and affect osteoblast maturation. A panel of 11 Runx2-targeting miRNAs (miR-23a, miR-30c, miR-34c, miR-133a, miR-135a, miR-137, miR-204, miR-205, miR-217, miR-218, and miR-338) is expressed in a lineage-related pattern in mesenchymal cell types. During both osteogenic and chondrogenic differentiation, these miRNAs, in general, are inversely expressed relative to Runx2. Based on 3'UTR luciferase reporter, immunoblot, and mRNA stability assays, each miRNA directly attenuates Runx2 protein accumulation. Runx2-targeting miRNAs differentially inhibit Runx2 protein expression in osteoblasts and chondrocytes and display different efficacies. Thus, cellular context contributes to miRNA-mediated regulation of Runx2. All Runx2-targeting miRNAs (except miR-218) significantly impede osteoblast differentiation, and their effects can be reversed by the corresponding anti-miRNAs. These findings demonstrate that osteoblastogenesis is limited by an elaborate network of functionally tested miRNAs that directly target the osteogenic master regulator Runx2.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
1091-6490
pubmed:author
pubmed:issnType
Electronic
pubmed:day
14
pubmed:volume
108
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
9863-8
pubmed:meshHeading
pubmed-meshheading:21628588-3' Untranslated Regions, pubmed-meshheading:21628588-Animals, pubmed-meshheading:21628588-Base Sequence, pubmed-meshheading:21628588-Blotting, Western, pubmed-meshheading:21628588-Cell Differentiation, pubmed-meshheading:21628588-Cell Line, pubmed-meshheading:21628588-Cell Lineage, pubmed-meshheading:21628588-Chondrocytes, pubmed-meshheading:21628588-Core Binding Factor Alpha 1 Subunit, pubmed-meshheading:21628588-Gene Expression Profiling, pubmed-meshheading:21628588-Gene Expression Regulation, pubmed-meshheading:21628588-Luciferases, pubmed-meshheading:21628588-Mice, pubmed-meshheading:21628588-MicroRNAs, pubmed-meshheading:21628588-NIH 3T3 Cells, pubmed-meshheading:21628588-Osteoblasts, pubmed-meshheading:21628588-Osteogenesis, pubmed-meshheading:21628588-RNA, Messenger, pubmed-meshheading:21628588-RNA Stability
pubmed:year
2011
pubmed:articleTitle
A program of microRNAs controls osteogenic lineage progression by targeting transcription factor Runx2.
pubmed:affiliation
Department of Cell Biology and Cancer Center, University of Massachusetts Medical School, Worcester, MA 01655, USA.
pubmed:publicationType
Journal Article, Research Support, N.I.H., Extramural