A program of microRNAs controls osteogenic lineage progression by targeting transcription factor Runx2

Ying Zhang, Rong Lin Xie, Carlo M. Croce, Janet L. Stein, Jane B. Lian, Andre J van Wijnen, Gary S. Stein

Research output: Contribution to journalArticle

261 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)9863-9868
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume108
Issue number24
DOIs
StatePublished - Jun 14 2011
Externally publishedYes

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Keywords

  • Chondrogenesis
  • Osteogenesis
  • Post-transcriptional regulation

ASJC Scopus subject areas

  • General

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